Steven D. Bines, M.D., Thomas R. Witt, M.D., Katherine Kopkash, M.D., Andrea Madrigrano, M.D.
1 A 35-year-old woman visits her physician after her initial mammogram, which was normal, and asks what her lifetime chance for the development of breast cancer is. She has no personal or family history of breast disease. Her menarche occurred at age 13, and her first child was born when she was 22. She has never taken oral contraceptives. Which is not a factor in estimating the Gail risk?
A Age
B History of previous breast biopsy
C Prior history of radiation exposure
D Age at menarche
E Age at first live birth
Ref.: 1-5
Comments
The American Cancer Society (ACS) in 2008 estimated that there would be 179,920 new cases of breast cancer in the United States and 40,730 deaths. The lifetime probability for the development of breast cancer is now estimated to be 1 in 8 (12.5%). After continuously increasing for more than 2 decades, breast cancer incidence rates in women decreased by 3.5% per year from 2001 to 2004, probably due in part to a slight decline in mammography utilization and a reduction in the use of hormone replacement therapy.
The Gail model is a validated breast cancer risk assessment tool that is primarily based on nonmodifiable breast cancer risk factors. It is a multivariate statistical model that uses age, age at menarche, age at first live birth, family history of breast cancer, and number of breast biopsies to estimate breast cancer risk in individuals without a previous history of breast cancer. It has been shown to accurately estimate the proportion of woman in whom breast cancer will develop when used in large groups. However, it performs poorly in discriminating between individual women in whom breast cancer will and will not develop. Although previous thoracic radiation therapy does increase breast cancer risk, it is not part of the Gail model. Other significant risk factors for breast cancer in women include previous biopsy specimens revealing atypical hyperplasia or lobular carcinoma in situ (LCIS), personal history of breast cancer, family history of breast cancer, and being a known carrier of a mutation in the BRCA1 or BRCA2 genes or a first-degree relative of an individual with a mutation.
Answer
C
2 With regard to the natural history of breast cancer, which of the following statements is true?
A On average, a 1-cm breast cancer has been present subclinically for approximately 1 year.
B Dimpling of the skin occurs as a result of glandular fibrosis and shortening of the Cooper ligaments.
C Skin edema in breast cancer is only a result of direct skin invasion by tumor.
D Lymph node metastasis first occurs in levels II and III of the axilla up to 20% of the time.
E Ipsilateral lung involvement occurs most often as a result of direct chest wall invasion.
Ref.: 6
Comments
Most breast cancers are estimated to have volume-doubling times of 2 to 12 months, thus suggesting that the average 1-cm tumor has been present for at least 5 years before clinical detection. Neither skin dimpling nor edema requires direct skin invasion. These conditions can result from fibrosis (with shortening of the Cooper ligaments) and lymphatic blockage in the subdermal tissues, respectively. The most common site of initial axillary lymph node metastasis is level I, which is inferior to the axillary vein and lateral to the pectoralis minor muscle. All forms of distant metastases, including ipsilateral lung involvement, are due to hematogenous spread. Lymph node metastasis first occurs in level II or III in 2% to 3% of patients, the so-called skip metastasis.
Answer
B
3 With regard to the natural history of breast cancer, which of the following statements is true?
A Virtually all patients with untreated breast cancer die within 2 years of their diagnosis.
B The likelihood of distant metastasis is related to the size of the primary tumor and involvement of the axillary nodes.
C The most common initial site for distant metastasis is the liver.
D Stage for stage, the survival rate for breast cancer in males is lower than that in females.
E Survival is longer in patients who undergo mastectomy than in patients who undergo breast conservation for stage I and II breast carcinoma.
Ref.: 5, 6
Comments
Breast cancer is a disease of wide biologic variability, and although the median survival in untreated patients is 2.7 years, nearly 20% of untreated patients survive 5 years and some as long as 15 years. The 5-year relative survival rate for stage 0 disease (carcinoma in situ with no regional node involvement or distant metastasis) is nearly 100%, whereas the 5-year survival rate for stage IV disease (distant metastasis) is 20%. There is an increased chance for distant metastasis in those with positive axillary nodes and large tumors. Therefore, adjuvant systemic therapy is recommended for these high-risk patients. The lung is the most common site of distant disease in patients dying of disseminated breast cancer. However, bone is the most common initial site of distant metastasis, followed by the lung, soft tissues, liver, and central nervous system. Male breast cancer accounts for 0.8% of all breast cancers, and the majority are invasive ductal carcinomas. When matched for age and stage, survival is similar to that in women. Multiple large randomized prospective trials (with follow-up now longer than 35 years) have shown that there is no survival advantage for mastectomy over breast conservation; however, the risk for local recurrence is slightly higher in those choosing breast conservation.
Answer
B
4 A 55-year-old woman is found on examination to have a 3-cm breast mass with palpable axillary lymph nodes. A modified radical mastectomy is performed, and pathologic evaluation reveals a 3.2-cm infiltrating ductal carcinoma with 5 of 15 axillary nodes positive for metastasis. Her review of systems is otherwise negative and findings on laboratory studies and basic imaging are normal. What is her tumor-nodes-metastasis (TNM) stage?
A T2N1M0
B T1N2M1
C T2N2M0
D T4N1M0
E T3N2M0
Ref.: 5
Comments
Breast cancer stage is determined by the results of pathologic evaluation of surgical resection specimens and imaging studies. It is classified with the tumor-nodes-metastasis classification system, which is based on a description of the primary tumor (T), the status of regional lymph nodes (N), and the presence of distant metastasis (M). The most widely used system is that of the American Joint Commission for Cancer (AJCC). T1 designates tumors up to 2 cm in size, T2 is used for those between 2 and 5 cm, T3 indicates tumors larger than 5 cm, and T4 is used for tumors of any size with extension to the chest wall or skin. N1 indicates metastasis to 1 to 3 axillary nodes or clinically occult internal mammary nodes (or both); N2 includes metastasis to 4 to 9 axillary nodes or clinically positive internal mammary nodes (without axillary metastasis); and N3 is used for metastasis to 10 or more axillary nodes, a combination of axillary and internal mammary nodes, or paraclavicular nodes. M1 designates evidence of distant metastasis.
Answer
C
5 A 58-year-old woman has a chronic erythematous, oozing, eczematoid rash involving her left nipple and areola. There are no palpable breast masses, and the findings on a recently obtained mammogram are normal. Which of the following recommendations is appropriate?
A Referral to a dermatologist
B Oral vitamin E and topical aloe and lanolin
C Biopsy
D Encouragement of the patient to buy a nonallergenic brassiere
E Routine clinical and mammographic follow-up in 1 year because findings on the current mammogram are normal
Ref.: 5, 6
Comments
Paget disease accounts for 1% or less of breast malignancies and is characterized clinically by nipple erythema and irritation with associated itching and may progress to nipple crusting and ulceration. A manifestation of this sort is very concerning, and therefore biopsy of the nipple is necessary. Delay in diagnosis of Paget disease of the breast is common because of the mistaken presumption that the findings represent a benign dermatologic condition. Pathologically, Paget cells are large, pale-staining cells with round or oval nuclei and large nucleoli and are located between the normal keratinocytes of the nipple epidermis. More than 97% of patients with Paget disease have underlying ductal carcinoma in situ (DCIS) or invasive breast carcinoma, but there is an accompanying mass in only 54% of patients. Treatment of Paget disease includes mastectomy with axillary staging or wide excision of the nipple and areola to achieve clear margins, possibly axillary staging, and radiation therapy.
Answer
C
6 Which of the following is not a characteristic of medullary breast cancer?
A Lymphocytic infiltrate
B Benign appearance on ultrasound
C High rate of lymph node metastasis
D Statistically better than average prognosis
E Usually manifested as a palpable mass
Ref.: 5, 6
Comments
Medullary breast cancer accounts for approximately 5% of breast cancers. It is usually manifested as a palpable mass with smooth borders on imaging that can mimic benign conditions. On ultrasound, medullary carcinoma often has smooth contours, homogeneous interior echogenicity, and posterior enhancement, which are the same findings that one would expect with a fibroadenoma. These tumors are characterized by an infiltrate of small mononuclear lymphocytes, are less likely to be associated with axillary node metastasis, and have a better than average prognosis.
Answer
C
7 A 34-year-old woman underwent wide local excision, axillary dissection, and radiation therapy (5000 cGy over a 5-week period) in her left breast for a node-positive, estrogen receptor (ER)-negative, 2-cm infiltrating ductal carcinoma 3 years earlier. She received four cycles of adjuvant chemotherapy with cyclophosphamide (Cytoxan) and doxorubicin (Adriamycin) at that time. The surgeon now performs a biopsy of a new 2-cm mass in the same breast, and it shows infiltrating ductal carcinoma. She has no other evidence of local, regional, or distant disease on imaging studies and clinical examination. Which of the following treatment plans is most appropriate?
A Left total mastectomy without axillary exploration
B Reexcision to free margins, sentinel lymph node biopsy, and a 5000-cGy “boost” to the breast
C A 5000-cGy “boost” to the breast and combination 5-fluorouracil–based chemotherapy
D Taxane-based chemotherapy alone
E Bilateral total mastectomy
Ref.: 5, 7, 8
Comments
The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial found that approximately 8.8% of patients treated by lumpectomy, axillary dissection, radiation therapy, and chemotherapy had a local recurrence by 10 years after initial treatment. A “salvage” mastectomy is usually required in these situations and results in long-term survival similar to that of patients who had a mastectomy performed as the primary operation. In the absence of palpable nodes, a second surgical axillary evaluation is unnecessary and hazardous. The effects of ionizing irradiation are cumulative and do not diminish with time, so additional radiation would lead to excessive toxicity in normal tissue in the irradiated area. Because local control is needed for this tumor, chemotherapy alone would be an inappropriate treatment option. Right total mastectomy is not indicated at this time based on the information provided.
Answer
A
8 Which characteristic of a positive axillary sentinel lymph node is not associated with additional positive nodes and distant recurrence?
A Node diameter greater than 1 cm
B Firmness on palpation
C Isolated tumor cells
D Nodal micrometastases
E Grossly irregular nodal border
Ref.: 9
Comments
Metastasis to regional lymph nodes is the most important prognostic factor in breast cancer patients. Sentinel lymph node biopsy has become a standard diagnostic procedure in clinically node-negative breast cancer patients. The standard nodal analysis includes both staining with hematoxylin and eosin and immunohistochemistry. Nodal micrometastases are considered to be 0.2 mm to 2 mm, whereas isolated tumor cells are less than 0.2 mm. A recently published prospective breast cancer study found that sentinel node micrometastases, but not isolated tumor cells, were associated with additional positive nodes and distant recurrence. Clinical evidence of lymph node involvement at the time of sentinel node surgery, whether by size, texture, or irregular borders, is associated with an increased likelihood of other nodes being involved. These data suggest that in the future, axillary lymph node dissection may be unnecessary in patients with isolated tumor cells but should be considered in patients with sentinel lymph node micrometastases.
Answer
C
9 A 39-year-old woman has an ill-defined 2-cm mass in the upper outer quadrant of her right breast. Mammography and ultrasound confirm this solid lesion. Ultrasound-guided fine-needle aspiration is performed, and cytologic evaluation reveals a highly cellular, monomorphic pattern. There are poorly cohesive intact cells, nuclear “crowding” with variation in nuclear size, radial dispersion and clumping of the chromatin, and prominent nucleoli. What is the diagnosis?
A Benign cyst contents
B Fibroadenoma
C Phyllodes tumor
D Carcinoma
E Fat necrosis
Ref.: 5
Comments
Fine-needle aspiration has become a routine part of the pathologic diagnosis of breast masses. The fluid and cellular material from the aspirate are either submitted in physiologically buffered saline or fixed immediately on slides in 95% ethyl alcohol. Cyst fluid is usually turbid and dark green or amber and can be discarded if the mass totally disappears and the fluid is not bloody. Fibroadenomas are benign solid tumors characterized by a proliferation of connective tissue and a variable component of ductal elements that may appear compressed by the swirls of fibroblastic growth. Phyllodes tumors are histologically similar to fibroadenoma, but the whorled stroma forms larger clefts lined by epithelium that resemble clusters of leaflike structures. Invasive carcinomas are recognized by their lack of overall architecture, by the infiltration of cells haphazardly into a variable amount of stroma, or by the formation of sheets of continuous and monotonous cells without respect for form and function of a glandular organ. Fat necrosiswill histologically show a lesion composed of lipid-laden macrophages, scar tissue, and chronic inflammatory cells.
Answer
D
10 A 42-year-old woman underwent lumpectomy and axillary dissection for a 2-cm, moderately differentiated, ER-negative infiltrating ductal carcinoma. Pathologic examination revealed adequate margins, and 1 of 19 lymph nodes was found to be positive for carcinoma. Which of the following treatment plans is most appropriate?
A Radiation alone
B Single-drug chemotherapy and radiation therapy
C Multidrug chemotherapy and radiation therapy
D Multidrug chemotherapy, radiation therapy, and tamoxifen
E Multidrug chemotherapy alone
Ref.: 5-7
Comments
Multiple randomized prospective studies have shown both disease-free and overall survival benefit for adjuvant chemotherapy in node-positive premenopausal women, the greatest advantage occurring in those with one to three positive nodes. Postmenopausal node-positive women have generally shown a more modest benefit. Multiple-drug therapy has consistently been more effective than single-drug therapy. Adding tamoxifen to the chemotherapy for node-positive premenopausal patients confers additional benefit when the cancer is ER positive, but it is not beneficial in ER-negative cancers. The use of radiation therapy in conjunction with surgery has allowed dramatic reductions in the extent of surgery required for local control of breast cancer. At 20 years of follow-up, local recurrence rates are approximately 8.8% for lumpectomy plus radiation as compared with 44% for lumpectomy alone.
Answer
C
11 Which of the following is not an indication for postmastectomy radiotherapy?
A T3 tumors
B Multicentric DCIS larger than 6 cm
C Four or more positive axillary lymph nodes
D Inflammatory breast cancer
E Gross extranodal extension
Ref.: 5, 7
Comments
For most patients with breast cancer, mastectomy provides effective local control and radiation therapy is not required. However, certain subsets remain at increased risk for local and regional recurrence and benefit from the ability of radiation to control any microscopic residual tumor. Adjuvant radiation therapy after mastectomy does decrease local-regional recurrences by up to two thirds, and some studies have shown an improvement in overall survival. Radiation therapy has many potential side effects as a result of irradiation of the chest wall, including skin ulceration, arm edema, rib fracture, radiation-induced pneumonitis, chest wall sarcoma, and cardiac toxicity. Therefore, most centers now recommend chest wall and nodal irradiation after mastectomy only for patients at increased risk for recurrence. This category includes those with multiple positive lymph nodes (more than four), patients with large cancers (>5 cm), aggressive histology (diffuse vascular invasion), and extranodal extension of breast cancer. Other indicators include positive surgical margins, inflammatory breast cancer, or involvement of the skin, fascia, or skeletal muscle. Extensive DCIS is not an indication for radiation therapy, provided that the margins of the mastectomy specimen are not involved.
Answer
B
12 Which of the following 5-year survival rates by stage for treated breast cancer is incorrect?
A Stage I: 95% to 100%
B Stage II: 80% to 90%
C Stage III: 50% to 70%
D Stage IV: 1% to 5%
E Stage Tis: 98% to 100%
Ref.: 5
Comments
The wide range of survival rates in patients with the same stages of breast cancer reflects the wide range of staging criteria used by various investigators, as well as the variability in biologic behavior among the differing subtypes of breast cancer within a given stage. Because of increasingly effective systemic therapies, patients with stage IV disease now have up to a 20% 5-year relative survival rate.
Answer
D
13 Which is not true regarding chronic granulomatous mastitis?
A Tuberculosis is a common granulomatous infection of the breast.
B Chronic granulomatous mastitis includes variants of ductal ectasia.
C It can be recognized on frozen section.
D It may be a sign of a systemic disorder.
E This classification is considered to be a descriptive diagnostic term.
Ref.: 7
Comments
Chronic granulomatous mastitis is a broad descriptive designation that includes variants of ductal ectasia, granulomatous infectious diseases, and idiopathic granulomatous conditions. It may be difficult to distinguish chronic granulomatous mastitis from ductal ectasia or from infectious granulomatous mastitis. Specific granulomatous infections such as tuberculosis may occur in the breast, although this is very uncommon; tuberculosis is responsible for approximately 0.025% to 0.1% of all surgically treated diseases of the breast. Recognition of granulomatous inflammation at the time of frozen section should prompt a search for the etiologic agent through culture. Granulomatous mastitis may be the initial sign of a systemic disorder such as Wegener granulomatosis. Sarcoidosis is another diagnostic consideration when granulomas are found in the breast. These conditions are often treated with corticosteroid therapy, with promising results.
Answer
A
14 A 75-year-old woman has a 1.2-cm mass in her right breast on physical examination that is found to be an infiltrating ductal carcinoma, ER/progesterone receptor (PR) positive, on core biopsy. Her axilla is clinically negative, as is her review of systems. She has multiple medical problems and wants to have as little done as possible. Which factor is not significantly associated with lymph node metastasis in elderly patients?
A Age
B Tumor location
C Tumor size
D Lymphovascular invasion
E Human epidermal growth factor receptor-2 (HER-2)/neu status
Ref.: 10
Comments
Nodal evaluation in elderly women with breast cancer remains controversial. The risk associated with lymph node evaluation must be balanced with the benefit of staging and local control. A recent large prospective multicenter trial found that on multivariate analysis, patient age, tumor size, and lymphovascular invasion were significant factors predicting lymph node metastasis. Patient race, palpable tumor, tumor grade, histologic subtype, and tumor location were not found to be significant. These findings suggest that some elderly breast cancer patients with a low likelihood of lymph node metastasis may be spared lymph node evaluation. HER-2/neu status is not an indicator of lymph node status.
Answer
B
15 A 42-year-old woman with no family history of breast cancer has an ill-defined thickening in the upper outer quadrant of her left breast. Her mammogram shows only a minimal increase in the fibroglandular markings in that area. Ultrasound examination reveals no mass lesion. One month later, the thickening is slightly more prominent, and the surgeon performs a biopsy of the area in question. The pathologic diagnosis is “stromal fibrosis,” with the comments describing increased fibrosis, ductal ectasia, periductal inflammation, and microcyst formation with no epithelial hyperplasia. What is the increase in likelihood that breast cancer will subsequently develop?
A Essentially none
B Three times
C Five times
D Ten times
E Twenty times
Ref.: 7
Comments
Stromal fibrosis has not been shown to increase the incidence of breast cancer. The presence of proliferative lesions, such as papillomatosis (multiple tiny ductal papillomas) or hyperplasia of the usual variety, very slightly increases the risk for breast cancer. Atypical hyperplasia increases the risk fourfold unless it accompanies a strong family history of breast cancer, in which case the risk is increased ninefold.
Answer
A
16 A 24-year-old woman who is 9 months postpartum has a tender, fluctuant area in her right breast near the areolar border. She denies fever or chills and has no other medical problems. What is the most appropriate treatment?
A Surgical incision and drainage
B Needle aspiration
C Multidrug antibiotics
D Core needle biopsy to exclude malignancy
E Needle aspiration and antibiotics
Ref.: 5, 11
Comments
Infections of the breast fall into two general categories, lactational infections (such as in this patient) and chronic subareolar infections associated with ductal ectasia. Lactation-related infections are thought to arise from entry of bacteria through the nipple and into the duct system and are characterized by erythema, tenderness, and less often, fever and leukocytosis. They are most frequently due to Staphylococcus aureus. In the past, these abscesses were often drained surgically, but the more recent literature supports antibiotics and needle aspiration of the abscess.
Answer
E
17 With regard to breast development, which of the following statements is true?
A Breast enlargement in male neonates is indicative of an underlying estrogen-secreting adrenal tumor.
B Accessory nipples can be found anywhere from the axilla to the groin.
C Extramammary breast tissue is not under the influence of the hormonal status of the patient.
D Inverted nipples in children suggest underlying breast cancer.
E Gynecomastia in a prepubertal boy requires excision.
Ref.: 5, 6
Comments
If the embryologic mammary ridge extending from the axilla to the groin fails to involute fully, accessory nipples (polythelia) can appear along this route. Accessory breast tissue (polymastia) is also seen frequently in the axilla and may enlarge during pregnancy and lactation, as well as during the response to normal fluctuations in the patient’s hormonal status during her menstrual cycle. Accessory breast tissue can be detected on mammography and may present differential diagnostic difficulties for both the mammographer and the clinician. Shortly after birth, both males and females may exhibit unilateral or bilateral breast enlargement, which is attributed to high levels of circulating maternal estrogen. These changes regress spontaneously during the neonatal period. In female infants, failure of one or both nipples to evert following birth and into adulthood leads to functional problems related to future breastfeeding but is unrelated to future breast cancer. Gynecomastia in prepubescent boys is usually a transient condition.
Answer
B
18 Which of the following is not true regarding magnetic resonance imaging (MRI) for evaluation of breast abnormalities?
A It is useful for finding the primary breast lesion in patients with positive axillary nodes but no mammographic evidence of a breast tumor.
B It is more accurate than mammography in diagnosing invasive lobular cancer.
C It is more accurate than mammography in assessing tumor extent in older women.
D Its sensitivity in detecting invasive cancer is greater than 90%.
E Its use as a screening tool is still under investigation.
Ref.: 5
Comments
Magnetic resonance imaging is increasingly being used for the evaluation of breast abnormalities. It is useful in finding the primary breast lesion in patients with malignant axillary nodes but no palpable or mammographic evidence of a primary breast tumor. MRI may be more accurate than mammography in assessing the extent of the primary tumor, particularly in young women with dense breast tissue, and in diagnosing invasive lobular cancer, and it may help determine eligibility for breast conservation. Use of MRI as a screening tool is still under investigation, but it appears promising for early detection of malignancy in patients with BRCA gene mutations. The sensitivity of MRI for invasive cancer is greater than 90%, but it is only 60% or less for DCIS.
Answer
C
19 With regard to current therapy for stage I and stage II breast cancer, which statement is true?
A The Halstead radical mastectomy has resulted in a cure rate superior to that of other surgical treatment options.
B Lumpectomy and radiation therapy are associated with a local recurrence rate of 25%.
C Oncotype DX assists in making decisions regarding chemotherapy in node-negative, ER-positive, HER-2/neu–negative cancers.
D Node-negative patients who undergo modified radical mastectomy have a survival advantage over those who choose lumpectomy, sentinel lymph node biopsy, and radiation therapy.
E There is no role for skin-sparing mastectomy in the treatment of invasive cancers.
Ref.: 6-8, 12
Comments
The two most commonly used modalities of definitive therapy for stage I and II breast cancer are (1) modified radical mastectomy, which preserves the pectoralis major muscle while excising all breast tissue, including the nipple and axillary nodal basin, and (2) wide local excision of the breast tumor (lumpectomy) and axillary evaluation (sentinel lymph node biopsy or axillary dissection, or both) in conjunction with postoperative whole-breast irradiation. A number of large randomized trials have shown no significant disease-free survival advantage for the more radical (pectoralis-removing) Halsted mastectomy. Lumpectomy plus radiation therapy is associated with a local recurrence rate of 14%. Oncotype DX is increasingly being used to determine how aggressive certain cancers are and can therefore help guide decisions regarding adjuvant therapy. Cyclin D1 has been implicated as an important oncogene in breast cancer, and overexpression of it correlates with the expression of ER, yet it has not yet been shown to have independent prognostic significance. There is consensus that p53 expression in breast cancer correlates with high tumor grade, indices of proliferation such as S-phase fraction and proliferating cell nuclear antigen staining, aneuploidy, and absence of ER and PR and therefore correlates with poor prognosis. In general, B cell lymphoma-2 expression is associated with a phenotype that has a favorable prognosis and correlates with the presence of ER, whereas B cell lymphoma-XL overexpression has an association with axillary lymph node positivity and high tumor grade. The National Surgical Adjuvant Breast and Bowel Project B-06 trial showed that regardless of nodal status, there was no difference in overall survival between patients undergoing modified radical mastectomy and those undergoing lumpectomy with surgical axillary staging and radiation therapy. A skin-sparing mastectomy can be performed for invasive cancer if immediate reconstruction is planned, and it does not have a detrimental effect on long-term survival or local recurrence rates.
Answer
C
20 Which of the following clinical characteristics of breast masses on physical examination is more suggestive of malignant than benign disease?
A Indistinct borders blending into surrounding breast tissue
B Excessive mobility within breast tissue
C Tenderness over a soft mass
D Tethering to underlying muscular structures
E Variability through the menstrual cycle
Ref.: 5, 6
Comments
Although there are many exceptions to the classic physical findings of breast cancer, the typical breast carcinoma is hard and has fairly distinct borders. Fixation to deeper structures is highly suggestive of malignancy. A smooth, rubbery, mobile mass is more suggestive of fibroadenoma. Fibrocystic disease may be manifested as a disk-like or polynodular thickening, with one or more of the borders blending indistinctly into the surrounding breast tissue. Tenderness over a soft breast mass is often found with breast cysts. Variability over the menstrual cycle is a benign feature.
Answer
D
21 Which of the following is not true regarding skin-sparing mastectomy?
A Involves the removal of 30% to 50% of breast skin
B May be appropriate for a central tumor that would require removal of the nipple/areola complex
C May be used for multifocal, minimal breast cancers
D Includes skin excision with 1-cm margins around the previous biopsy site or scar overlying the index neoplasm
E Requires skin excision (marginal only) of the nipple/areola complex
Ref.: 7
Comments
Wide skin excision is used routinely in every radical and modified mastectomy and often includes excision in excess of 30% to 50% of the breast skin. “Skin-sparing” mastectomy, or limited skin excision, can be defined as excision of the nipple/areola complex, the skin around the biopsy site, and the skin within 1 to 2 cm of the tumor margin. This technique usually sacrifices only 5% to 10% of the breast skin, and the excision is usually closed primarily or in association with breast reconstruction. The extent of breast skin excision required with mastectomy has decreased as locoregional control measures have improved over the last 60 years. Patients who are not candidates for lumpectomy and postoperative radiation therapy but are candidates for skin-sparing mastectomy include those with multicentric disease, invasive carcinoma associated with an extensive intraductal component, T2 tumors with a difficult-to-interpret mammograms, and central tumors that would require removal of the nipple/areola complex. The skin-sparing mastectomy may include sentinel lymph node biopsy as indicated and, if histologically positive, axillary lymph node dissection to be completed synchronously.
Answer
A
22 With regard to phyllodes tumors of the breast, which statement is incorrect?
A It is histologically characterized by epithelial cystlike spaces.
B Examination reveals a firm, mobile, well-circumscribed mass.
C Ten percent to 15% are malignant.
D The benign version can grow aggressively and recur locally.
E It commonly metastasizes to lymph nodes.
Ref.: 5-7
Comments
Although only approximately 10% of all phyllodes tumors (also called cystosarcoma phyllodes) are malignant, they are still the most common primary sarcoma of the breast. The benign variant of cystosarcoma is considered by many to be a “giant fibroadenoma” and, accordingly, is usually manifested clinically as a solitary, discrete, mobile mass within the breast (generally quite a bit larger than the average fibroadenoma). The diagnosis of malignancy in phyllodes tumor is at times difficult because of the poor correlation between histologic features and clinical behavior. The benign and malignant varieties may be differentiated by counting the number of mitoses seen per high-power field, in addition to observing other features. If the tumor is histologically benign, wide local excision is considered adequate treatment. Even when benign, phyllodes tumors have a high frequency of local recurrence, and therefore careful long-term follow-up is essential. In the malignant variety, lymph node involvement is uncommon because these tumors usually metastasize through the bloodstream, most often to the lung. Therefore, total mastectomywithout axillary dissection may be indicated; although for small malignant lesions, wide excision with 2-cm margins may be appropriate. Malignant cystosarcoma has no significant incidence of multicentricity within the breast (unlike ductal or lobular carcinoma).
Answer
E
23 With regard to breast carcinoma in men, which statement is true?
A It is detected most commonly in men 60 to 70 years old.
B Gynecomastia is a risk factor.
C It is commonly associated with a mutation in the BRCA1 gene.
D The prognosis is worse stage for stage than for women.
E Sentinel lymph node biopsy is contraindicated.
Ref.: 5
Comments
Breast cancer infrequently occurs in men; it accounts for just 0.8% of all breast cancers and less than 1% of all newly diagnosed cancers in men. The median age at diagnosis is 68 years, 5 years older than in women. Risk factors include increasing age, radiation exposure, factors related to abnormalities in estrogen and androgen balance (testicular disease, infertility, obesity, and cirrhosis), and genetic predisposition, including Klinefelter syndrome, family history, and BRCA2 gene mutations. Ninety percent of male breast cancers are invasive ductal carcinomas. The majority of men with breast cancer have a breast mass, and when matched for age and stage, survival is similar to that in women. Treatment of carcinoma in the male breast is similar to that in the female breast, and prognostic factors include nodal involvement, tumor size, histologic grade, and hormone receptor status.
Answer
A
24 With regard to breast cancer screening, which of the following is not a current recommendation of the ACS?
A Monthly breast self-examinations are strongly encouraged and should be performed the week before menses.
B Screening mammograms should be performed yearly in women older than 40 years.
C Women 20 to 30 years of age should undergo clinical breast examinations at least every 3 years.
D Women with greater than a 20% lifetime risk for the development of breast cancer should undergo MRI and mammographic screening yearly.
E Women 40 years and older should have yearly clinical breast examinations.
Ref.: 1
Comments
Research has shown that routine breast self-examination plays only a small role in breast cancer detection in comparison to being detected by chance or by physician examination or breast imaging. Therefore, breast self-examination should be discussed with patients as an option once they are in their 20s but is not a recommendation at this time. Women 40 years and older should undergo screening mammography every year and should continue to do so for as long as they are in good health. Women in their 20s and 30s should have a clinical breast examination as part of a periodic health examination by a health professional at a minimum of every 3 years. After the age of 40, women should have a breast examination by a health professional every year. Women at high risk (>20% lifetime risk) should undergo magnetic resonance imaging and mammography yearly. Women at moderately increased risk (15% to 20% lifetime risk) should talk with their doctors about the benefits and limitations of adding MRI screening to their yearly mammogram. Yearly MRI screening is not recommended for women whose lifetime risk for breast cancer is less than 15%.
Answer
A
25 Modern therapy for breast cancer focuses on molecular markers to help guide treatment strategies. Which of the following statements is correct?
A Carriers of the BRCA2 mutation are more likely to have triple-negative cancers.
B HER-2–positive cancers are unlikely to respond to treatment with trastuzumab.
C ER-positive/HER-2–negative patients should be treated with endocrine therapy.
D All breast cancers are sensitive to endocrine therapy.
Ref.: 5
Comments
Before discovery of the ER, all breast cancers were thought to be sensitive to endocrine therapy. Clinical trials and laboratory research established that only cancers containing ER (ER-positive cancers) respond to endocrine treatments. Furthermore, because binding of estrogen to its receptor induces progesterone receptor expression, the presence of PRs correlates with response to endocrine therapy. The presence of both receptors in a tumor is associated with an almost 80% chance of favorably responding to hormone blockade. Recently, the uniqueness of tumors that are ER negative, PR negative, and HER-2 negative has been investigated, and these triple-negative cancers express proteins in common with myoepithelial cells at the base of mammary ducts and therefore are also called basal-like cancers. Women who carry a disease-associated mutation in BRCA1 (but not BRCA2) are much more likely to contract a basal-like cancer than other subtypes. Human epidermal growth factor receptor-2 (or the erb-B2/neu protein) is a product of the erb-B2 gene and is amplified in about 20% of human breast cancers. Trastuzumab is a humanized antibody directed against the extracellular domain of the surface receptor and is effective treatment of HER-2–positive breast cancer.
Answer
C
26 A 57-year-old woman with a 1.5-cm infiltrating ductal carcinoma is found to be ER negative, PR negative, and HER-2/neu positive. She comes to your office to discuss treatment options. What would you recommend?
A Modified radical mastectomy alone
B Wide local excision, radiation therapy, and tamoxifen
C Simple mastectomy, sentinel lymph node biopsy, trastuzumab (Herceptin), and tamoxifen
D Modified radical mastectomy and adjuvant chemotherapy
E Wide local excision, sentinel lymph node biopsy, radiation therapy, and adjuvant chemotherapy with trastuzumab
Ref.: 5
Comments
In current practice, lumpectomy (wide local excision) is considered in cases in which the tumor can be excised to clear margins and leave an acceptable cosmetic result. Randomized trials have studied breast conservation for tumors up to 5 cm in size. Patients who undergo lumpectomy followed by radiation therapy have the same survival rate as do those who undergo modified radical mastectomy. Sentinel lymph node biopsy is an acceptable method of staging the axilla in breast cancer patients without clinically suspicious lymph nodes. Because the patient is ER and PR negative, she would not derive any benefit from treatment with tamoxifen. However, she is HER-2/neu positive and would therefore benefit from treatment with tratuzumab. Recent studies have shown that the addition of trastuzumab to conventional chemotherapy significantly reduces the rate of recurrence (almost a 50% reduction).
Answer
E
27 A 64-year-old woman underwent modified radical mastectomy without reconstruction 10 years earlier for a 3-cm, node-positive, ER-negative, infiltrating ductal carcinoma. She comes to you with a 2-cm immobile nodule in her scar. Which of the following statements is false?
A The patient should be restaged to detect any distant disease.
B Wide local excision followed by radiotherapy is appropriate if no distant disease is detected.
C There is level I evidence supporting a survival advantage in all age groups if chemotherapy is given.
D Local recurrence following mastectomy occurs in approximately 5% of patients.
E If metastatic disease is found, chemotherapy is favored over wide local excision alone.
Ref.: 7
Comments
Local recurrence of breast cancer following mastectomy occurs in approximately 5% of patients. Local excision plus irradiation is appropriate treatment for this patient. In older patients, the benefits of chemotherapy are generally less, and the ability to deliver optimal therapy is made more difficult by the presence of other impairments. In elderly patients, the decision to administer adjuvant chemotherapy is made on an individual basis since there are no firm results from clinical trials. Chest wall recurrence in this setting is often eventually accompanied by metastatic disease, even though initial evaluation may not detect it.
Answer
C
28 A 32-year-old woman who is 10 weeks pregnant has a palpable 2.5-cm mass in the upper outer quadrant of her right breast. The mass is not visualized on ultrasound. Which of the following management options is appropriate?
A Reassurance of the patient that this is probably benign in nature
B Reexamination 1 month after delivery
C Cyst aspiration and, if no fluid is obtained, reassurance of the patient
D Palpation-guided core needle biopsy
E Simple mastectomy
Ref.: 5, 7
Comments
See Question 29.
Answer
D
29 Core needle biopsy in the pregnant patient in Question 28 demonstrates an infiltrating ductal carcinoma, grade 3, ER negative, HER-2/neu negative. Further evaluation reveals a suspicious, palpable 1.5-cm right axillary mass that is positive on fine-needle biopsy. What is the most appropriate next step in her treatment?
A Chemotherapy and radiation therapy
B Modified radical mastectomy followed by chemotherapy
C Lumpectomy, axillary dissection, and radiation therapy
D Simple mastectomy with sentinel lymph node biopsy and chemotherapy
E Lumpectomy, axillary dissection, and immediate radiation therapy
Ref.: 5, 7
Comments
Stage for stage, the prognosis of breast cancer is the same in pregnant as in nonpregnant women. However, the overall prognosis for pregnant women is worse because they tend to initially be seen with a more advanced stage. Reluctance to evaluate breast masses in pregnant women on the part of both the patient and her physician is a contributing factor. The evaluation and treatment of breast masses must not be delayed because of pregnancy. Diagnostic mammograms can be performed safely in pregnant women with proper shielding of the uterus. However, radiation therapy, even with proper shielding, is associated with a significant incidence of fetal injury and is contraindicated. Mastectomy is usually appropriate during early and middle pregnancy. During the third trimester, breast preservation may be considered if early delivery after confirmation of fetal maturity would facilitate prompt commencement of whole-breast irradiation. This patient has a suspicious axillary node and is therefore not a candidate for sentinel lymph node biopsy. It is worth noting that there have been no reported consequences to either the mother or the fetus from injections of technetium sulfur colloid or isosulfan blue, which are the two agents that may be injected during sentinel lymph node biopsy. This does not imply that there is no risk, simply that none have been reported to date. Chemotherapy has been given safely to patients in the second trimester. For patients in the second and third trimester in whom breast cancer is diagnosed, breast conservation therapy can be an option, with radiation therapy being delayed until after delivery.
Answer
B
30 A 40-year-old woman has a mammogram showing extensive microcalcifications involving the entire upper aspect of her right breast. Stereotactic biopsy is performed, and pathologic analysis reveals grade 3 DCIS with comedo features. What is the appropriate management?
A Total mastectomy with sentinel lymph node biopsy
B Wide local excision alone
C Modified radical mastectomy
D Wide local excision with radiotherapy
E Radiotherapy alone
Ref.: 5, 6
Comments
See Question 31.
Answer
A
31 In the patient in Question 30, the operating surgeon performed a total mastectomy. Final pathologic review of the breast showed extensive DCIS and multiple foci of infiltrating ductal carcinoma, with the largest foci being 1.5 cm, ER positive, and HER-2/neu negative with a negative sentinel node. What is the next best step in the management of this patient?
A Sentinel lymph node biopsy
B Chemotherapy
C Tamoxifen alone
D Axillary dissection
E Radiotherapy
Ref.: 5
Comments
Ductal carcinoma in situ is a heterogeneous lesion morphologically, and pathologists recognize four broad categories: papillary, cribriform, solid, and comedo. DCIS is recognized as discrete spaces surrounded by basement membrane that are filled with malignant cells and usually with an identifiable, basally located cell layer made up of presumably normal myoepithelial cells. The solid and comedo types of DCIS are generally higher-grade lesions and probably invade over a shortened natural history. DCIS frequently coexists with invasive cancers. In current practice, reasons to select total mastectomy for the treatment of DCIS include the following: diffuse suspicious mammographic calcifications suggestive of extensive disease, inability to obtain clear margins on wide excision, likelihood of a poor cosmetic result after wide excision of involved tissue, patient not motivated to preserve her breast, and contraindications to radiation therapy. Sentinel node biopsy is currently recommended when mastectomy is performed for DCIS because up to 10% of patients with DCIS on diagnostic biopsy will be found to have invasive cancer in their mastectomy specimen. The addition of sentinel lymph node biopsy to mastectomy adds minimal morbidity, and because sentinel node mapping is no longer possible after mastectomy, it may avoid the need for axillary dissection if invasive cancer is identified later. If the axillary lymph nodes are found to be positive for cancer, this patient should undergo chemotherapy. Because her tumor is ER positive, she is also a candidate for adjuvant endocrine therapy, such as tamoxifen.
Answer
D
32 A 44-year-old woman has a tender, movable mass in the 12-o’clock position of her left breast. A mammogram shows a 2.5-cm, well-circumscribed density in the palpable area of concern. Ultrasound shows an anechoic, well-circumscribed mass with increased through-transmission. What is the appropriate first step in treatment?
A Excisional biopsy
B Ultrasound-guided core needle biopsy
C Tamoxifen
D Fine-needle aspiration
E Magnification and compression mammographic views of the lesion
Ref.: 5
Comments
Cysts within the breast are fluid-filled, epithelium-lined cavities that may vary in size from microscopic to large, palpable masses. A palpable cyst develops in at least 1 in every 14 women. Cysts are influenced by ovarian hormones, a fact that explains their variation with the menstrual cycle. Most cysts occur in women older than 35 years. A palpable mass can be confirmed to be a cyst by aspiration or ultrasound. Cyst fluid can be straw colored, opaque, or dark green and may contain flecks of debris. On ultrasound, cysts are round with smooth borders, have a paucity of internal sound echoes, and exhibit increased through-transmission of sound with enhanced posterior echoes. If the palpable mass disappears completely after aspiration and the cyst contents are not grossly bloody, the fluid need not be sent for cytologic analysis. If the cyst recurs, sending fluid for cytologic evaluation is justified. Surgical removal of a cyst is usually indicated if the cytologic findings are atypical or suspicious for malignancy or if the cyst continues to recur.
Answer
D
33 A 53-year-old woman with no family history of breast cancer detects a well-defined, 2-cm mass in the upper outer quadrant of her right breast. Mammography reveals only dense breast tissue, and findings on ultrasound are unremarkable. What is the next step in the management of this patient?
A Mammography and ultrasonography are extremely sensitive, so you can reassure her that the lesion is benign.
B Advise her to return for reevaluation in 3 months.
C Perform a core needle biopsy in the office.
D Order a breast MRI.
E Schedule her for an excisional biopsy.
Ref.: 7, 13
Comments
Most patients with breast cancer do not have a family history, so any palpable mass requires investigation. Either needle aspiration or core needle biopsy of a solid mass would be acceptable as an initial diagnostic step. A major goal of modern breast medicine is to minimize the number of patients with benign lesions who undergo open surgical breast biopsy for diagnosis. There are relatively few patients for whom excisional biopsy should be the initial procedure for diagnosis. For patients with a diagnosis of breast cancer, the goal is to make the diagnosis with a needle and to go to the operating room one time for definitive treatment. A definitive diagnosis of breast cancer made from a minimally invasive needle biopsy specimen permits optimal preoperative work-up, patient counseling, and surgical planning. Percutaneous histologic tissue acquisition techniques include large-core biopsy (typically 12 to 14 gauge), vacuum-assisted biopsy (typically 7 to 11 gauge), and larger-tissue acquisition methods. Dense breast tissue decreases the diagnostic sensitivity of mammography and can easily obscure a carcinoma. The absence of mammographic visualization in the presence of a palpable mass does not diminish the need for tissue diagnosis. In fact, up to 10% of breast cancers are found in women with a “negative” mammogram. Delaying evaluation of a well-defined mass for 3 months is ill advised. Magnetic resonance imagingis a very sensitive diagnostic tool, but at this point in evaluation of this lesion, a negative MRI result would not obviate the need for biopsy.
Answer
C
34 A 33-year-old asymptomatic woman is referred to the clinician with abnormal findings on a mammogram. No masses are palpable in either breast. The mammogram shows a tight cluster of microcalcifications at the 2-o’clock position in her left breast. Magnification compression views show at least 20 tiny, irregular calcifications in a 2-cm area that vary in shape and density with no associated mass lesion. There are no other calcifications present in either breast. Which of the following is the most likely diagnosis?
A LCIS
B Fibroadenoma
C Infiltrating ductal carcinoma
D DCIS (intraductal)
E Fibrocystic changes
Ref.: 7, 14
Comments
Mammographic calcifications are a hallmark of early breast cancer, particularly DCIS, but the common causes of calcifications identified on mammography are varied. Specific patterns have been identified that are often associated with and predictive of these pathologic processes. Parenchymal calcifications (i.e., those indicative of a pathologic breast process) occur in the lobar ductal system and in the terminal ductal lobular unit. Certain patterns of ductal calcification are almost pathognomonic of ductal carcinoma in situ, as is a specific bilateral pattern seen with plasma cell mastitis. One mammographic feature common to both high-grade DCIS and plasma cell mastitis is the appearance of calcium in a linear, branching pattern. Evenly scattered calcifications, more often than not bilateral, are indicative of a lobular process. This pattern is the one most commonly encountered and is indicative of either active or involutional fibrocystic change. Clustered calcifications, whether single or multiple, present a diagnostic dilemma because of the varied pathologic processes that give rise to this pattern. Close scrutiny of these areas on magnification views is required to delineate the finer characteristics of the calcifications. Coarse, granular-appearing calcifications are seen with partially calcified fibroadenomas and papillomas, fibrocystic change, and low- to intermediate-grade DCIS. Powdery calcifications are seen with sclerosing adenosis, with or without atypia, and low-grade DCIS. Large, coarse calcifications (popcornlike) are classically associated with a degenerating fibroadenoma and are readily discernible on mammography. Lobular carcinoma in situ and invasive lobular carcinoma are often mammographically featureless. The clustered geographic distribution and characteristics of the calcifications described in this scenario make a diagnosis of DCIS more likely than that of an invasive carcinoma, which often has an associated mass lesion seen on mammography.
Answer
D
35 A 47-year-old woman with a history of breast pain has a recent onset of nonspontaneous, bilateral, green nipple discharge from multiple ducts. She has generalized bilateral tenderness and no palpable mass on breast examination. The discharge is Hemoccult negative. Findings on mammography and ultrasound are unremarkable. Which of the following is the most appropriate first step in management?
A Schedule MRI.
B Perform an ultrasound-guided core biopsy.
C Reassure the patient.
D Obtain a galactogram.
E Excise the major retroareolar ducts.
Ref.: 7
Comments
Nipple discharge and breast tenderness are common complaints associated with mammary duct ectasia and fibrocystic change. Bilateral versus unilateral, multiple duct versus single duct, expressible (nonspontaneous) versus spontaneous, and colored (nonbloody) versus clear or bloody fluid are all strongly suggestive of a benign cause of the discharge. Accordingly, surgery would be inappropriate in this case. Reassurance is the appropriate management decision in this context, particularly in light of the clinical characteristics of the nipple discharge and the negative mammographic and physical examination findings. If the drainage is bloody, serous, or watery, further diagnostic work-up is indicated to determine the cause of the discharge. Although such discharges demand evaluation, the cause is often benign (commonly an intraductal papilloma or papillomatosis). Even though some surgeons prefer a preoperative contrast-enhanced radiograph of the involved duct (a galactogram) as a guide, the blood-distended duct is usually identifiable and can be removed through a circumareolar incision or lacrimal probe-guided terminal duct excision. If either preoperative or intraoperative ultrasound imaging is available, this modality can be used in real time to facilitate identification of the distended duct and to precisely map the area of operative excision. More recently, ductoscopy has been added as a tool for the evaluation of clinically worrisome nipple discharge.
Answer
C
36 With regard to pure tubular carcinoma, which of the following is true?
A Lymph node involvement is seen in 25% of cases.
B It is a highly aggressive, frequently fatal carcinoma.
C It tends to be ER negative.
D Neoadjuvant chemotherapy should be strongly considered.
E Stage for stage, it has a more favorable prognosis than other forms of ductal carcinoma.
Ref.: 7
Comments
When tubular carcinoma is present in its pure form, distant metastatic potential is highly unlikely. The diagnosis is made when characteristic angulated tubules, composed of cells with low-grade nuclei, constitute at least 90% of the carcinoma. Tubular carcinoma has a better prognosis than other varieties of infiltrating ductal cancer, and one classic study showed that all patients studied whose carcinoma was composed purely of the characteristic low-grade, angulated tubules survived at least 15 years, regardless of tumor size. Tubular carcinoma represents only about 3% to 5% of all invasive carcinomas, has the biologic correlates of a low-grade cancer (ER positive, diploid, low S phase, no expression of c-erbB-2), and is more likely to occur in older patients. The survival of patients with tubular carcinoma is generally similar to that of the general population, and systemic adjuvant therapy may be avoided in these patients. For selected cases of pure tubular carcinoma removed with an adequate negative margin, mastectomy, radiation therapy, or even axillary lymph node staging may be unnecessary.
Answer
E
37 A 39-year-old woman with no family history of breast cancer underwent excisional biopsy of a 2-cm breast mass. Histologic sections showed fibrosis, ductal ectasia, atypical lobular hyperplasia, and multiple foci of LCIS present at the medial, superior, and inferior margins. Which of the following statements is false?
A At a minimum, she needs to undergo reexcision to achieve negative margins.
B Tamoxifen can decrease risk for the future development of invasive cancer by 50%.
C If breast cancer develops, it would most likely be a ductal carcinoma.
D LCIS is typically not visible on mammography but is discovered incidentally on biopsy.
E LCIS is often multicentric and bilateral.
Ref.: 5, 7
Comments
Lobular carcinoma in situ is a histologic finding that is usually seen in tissue from a biopsy specimen of some other lesion. It represents a risk marker that predicts up to a ninefold increase in the chance for the development of breast cancer. Atypical lobular hyperplasia alone increases the risk fourfold. Acquisition of free margins is not necessary since LCIS is now not considered to be a malignant lesion but more of a risk factor for the development of breast cancer. Either infiltrating lobular or infiltrating ductal carcinoma may develop in this patient, with infiltrating ductal carcinoma being the more likely type. Less aggressive management is typically performed for this kind of lesion and consists of close follow-up with periodic physical examination and bilateral mammograms or the use of tamoxifen as chemoprevention, which has resulted in a nearly 50% reduction in risk for the development of breast cancer. LCIS is usually multicentric and often found in both breasts.
Answer
A
38 Which of the following statements is true regarding breast conservation surgery?
A Sixty percent of locally recurrent breast cancers develop at or near the site of the original breast cancer.
B Intraoperative radiotherapy (IORT) targeted to the tumor bed permits breast-conserving surgery and radiotherapy to be completed in one sitting.
C IORT is significantly more expensive than MammoSite balloon catheter brachytherapy.
D One known disadvantage of delivering radiotherapy at the time of breast cancer resection is increased toxicity to adjacent tissues.
E IORT can be repeated as needed.
Ref.: 15
Comments
The TARGIT trial (targeted intraoperative radiation therapy) is a phase III, prospective, randomized trial comparing single-fraction targeted intraoperative radiotherapy with conventional whole-breast external beam radiotherapy for the management of early-stage invasive breast cancer. Inclusion criteria for the trial include age 35 years and older and operable invasive breast cancer (T1-3, N0-1, M0) suitable for breast-conserving surgery. The principal objective of the trial is to determine whether single-fraction IORT targeted to the tumor bed provides equivalent local control as conventional therapy. In June 2010, the first phase initial results showed that IORT was equally effective at controlling recurrence. Toxicity was lower in the target group. However, the trial was limited to patients older than 45 and the tumor size was 3 cm or less. Randomized trials have shown that approximately 90% of locally recurrent breast cancers develop at or near the site of the original breast cancer. IORT is a form of accelerated partial-breast irradiation in which the entire radiotherapy dose is given intraoperatively, typically at the time of tumor removal. Spherical applicators are used that conform the breast tissue around the radiation source to permit delivery of a uniform field of radiation to a prescribed tissue depth. Chest wall and skin can be protected by tungsten-impregnated silicone barriers, which provide 93% shielding and minimize pulmonary, cardiac, and skin toxicity. Other advantages of IORT include convenience in that breast-conserving surgery and radiotherapy are completed in one sitting while the patient is still under anesthesia, accurate dose delivery because the radiation dose is directed to the surgical margins, and lower cost (IORT is a third the cost of MammoSite balloon catheter brachytherapy). Important limitations of IORT are the possible need for additional radiotherapy (repeated IORT is not permitted, so if inadequate surgical margins are found after IORT, external beam therapy may be required), lack of pretreatment pathologic review, and concern that this modality may be subtherapeutic and leave patients at elevated risk for local recurrence.
Answer
B
39 With regard to asymptomatic, nonpalpable, mammographically detected breast masses, which of the following statements is true?
A The mass should be excised if it is found in a woman older than 40 years.
B Unless the mass is painful, it can be followed with a mammogram in 6 months.
C Ultrasound is helpful in further defining breast lesions.
D Imaging-guided biopsy is contraindicated.
E Masses with a small, well-defined border and a “halo” sign around them are always benign.
Ref.: 5, 7
Comments
Mammographic abnormalities that cannot be detected by physical examination include clustered microcalcifications and areas of abnormal density (masses, architectural distortions, and asymmetries). The Breast Imaging Reporting and Data System (BI-RADS) is used to categorize the degree of suspicion of malignancy for a mammographic abnormality. To avoid unnecessary biopsies for low-suspicion mammographic findings, probably benign lesions are designated BI-RADS 3 and are monitored with a schedule of short-interval mammograms over a 2-year period. Imaging-guided biopsy is performed only for lesions that progress during follow-up; this can be done by image-guided core needle biopsy or image-guided wire localization followed by surgical excision. Ultrasound is useful in establishing whether a lesion detected by other modalities is solid or cystic and in determining the contour and internal properties of a lesion. Smooth, rounded masses cannot be assumed to be benign even if previous mammograms demonstrate a stable appearance over a long period. Some malignant tumors, including mucinous and medullary carcinoma or cystosarcoma phyllodes, can have a benign appearance on both ultrasound imaging and mammography.
Answer
C
40 A 38-year-old asymptomatic woman with normal findings on examination comes to see you after a stereotactic biopsy. She was not given any results, but she brought her pathology slides with her (Figure 14-1). What is the best surgical procedure for her condition?
A Modified radical mastectomy
B No surgical intervention necessary
C Bilateral total mastectomy without axillary dissection
D Lumpectomy and sentinel lymph node biopsy
E Lumpectomy alone
Figure 14-1
Ref.: 5-7
Comments
The hyperchromatic nuclei in a fairly uniform population of neoplastic-appearing cells filling and distending the ducts, along with sharply defined punched-out (Swiss cheese) spaces, are typical of a cribriform intraductal carcinoma. In contrast to a comedo pattern of intraductal carcinoma, this lesion can often be treated by excision to free margins and close follow-up. However, if free margins are not obtained, the rate of recurrence is high. Even if free margins are achieved, the lesion occasionally recurs in an invasive form. If the patient is unwilling to accept that small chance, total mastectomy or irradiation is appropriate, even though it may be overtreatment. Axillary dissection is unnecessary, and the long-term survival rate following mastectomy is essentially 100%.
Answer
E
41 Assuming that it is the same patient as listed in Question 40, how would your recommendations change if instead the slide in Figure 14-2 were the one she presents to you?
A Total mastectomy
B No surgical intervention necessary
C Bilateral total mastectomy with axillary dissection
D Lumpectomy and sentinel lymph node biopsy
E Lumpectomy alone
Figure 14-2
Ref.: 5-7
Comments
The nests of epithelial cells invading the stroma in random fashion, with a suggestion of tubule formation, are typical of infiltrating ductal carcinoma. Lumpectomy with sentinel lymph node biopsy followed by breast irradiation is the most appropriate treatment of those listed. Total mastectomy or lumpectomy alone fails to assess the axilla for staging, and bilateral total mastectomies with axillary dissection would be considered overtreatment.
Answer
D
42 Which of the following factors does not influence the choice of systemic adjuvant therapy for invasive breast cancer?
A Tumor size
B DNA ploidy
C HER-2/neu
D Axillary node status
E ER status
Ref.: 5
Comments
Metastatic disease is the primary cause of death from breast cancer. Patients who benefit from chemotherapy or hormonal therapy do so because metastasis is prevented, cured, or delayed. Currently, the recommendation for adjuvant systemic therapy is based on consideration of tumor size, HER-2/neu status, nodal status, ER status, and age or menopausal status. In patients with node-negative cancer, certain groups may suffer higher relapse rates, and the absolute benefits of chemotherapy are greater. Poor prognostic signs include tumor size greater than 2 cm, poor histologic and nuclear grade, absence of hormone receptors, high proliferative fraction, and overexpression of certain oncogenes such as HER-2/neu. When trastuzumab (Herceptin) is used in patients with HER-2–positive breast cancers, there is a 50% reduction in recurrence. In general, all node-positive tumors require chemotherapy. In women with ER-positive breast cancer, 5 years of tamoxifen or an aromatase inhibitor after surgical treatment nearly halves their recurrence rate and reduces breast cancer mortality by a third. Oncotype DX is a diagnostic test that assesses the tumor tissue and estimates the likelihood that invasive breast cancer will return or recur after treatment. This test looks at a group of 21 genes within a woman’s tumor sample—16 cancer genes and 5 control genes—to see how they are expressed or how active they are. The results of the test are reported as a quantitative Recurrence Score, which is a score between 0 and 100 that correlates with the likelihood of a woman’s chance of having her cancer return and the likelihood that she will benefit from adding chemotherapy to her hormonal therapy.
Answer
B
43 Which of the following is not a germline mutation associated with a higher incidence of breast cancer?
A APC
B BRCA1
C BRCA2
D p53
E PTEN
Ref.: 7
Comments
All of the choices are germline mutations. A germline mutation is a mutation that exists in every cell of the body and is therefore capable of being passed to the offspring via the sperm or egg. The APC gene is involved in regulation of cell growth and, when inherited in mutated form, leads to familial adenomatous polyposis and an increased incidence of colon cancer; it does not increase the risk for breast cancer. The predominant genes responsible for hereditary breast cancer are BRCA1 and BRCA2. Women who carry a germline mutation in either of these genes have about an 85% likelihood of breast cancer developing by the age of 70, although most cancers occur before 50 years of age. Women with these mutations also have an increased risk (30% to 60%) for the development of ovarian cancer. Inherited mutations of the p53 gene result in Li-Fraumeni syndrome, which is associated with the development of a number of malignancies, including breast cancer, sarcomas, brain tumors, adrenocortical carcinomas, and leukemia. Germline mutations in the PTEN gene are associated with Cowden disease, which is a hereditary disorder (also known as multiple hamartoma syndrome) that is inherited as an autosomal dominant trait and is characterized by distinctive mucocutaneous lesions and cancer of the breast, thyroid, and female genitourinary tract.
Answer
A
44 A germline mutation in BRCA1 or BRCA2 is associated with all of the following characteristics except:
A Autosomal dominant transmission
B High incidence of breast and ovarian cancer in women
C Higher than average incidence of breast cancer in men
D Incomplete penetrance
E Late-onset breast cancer
Ref.: 7
Comments
Mutations in BRCA1 or BRCA2 result in a higher incidence of breast and ovarian cancer. The risk for breast cancer is about 85% in individuals who carry the mutation and have a family history of breast cancer. The risk for ovarian cancer is about 40% with BRCA1 mutations and 20% with BRCA2 mutations. Breast cancer will develop in about 10% of males with BRCA2 mutations. These genes are incompletely penetrant; that is, some mutation carriers can live to old age without the development of cancer. The mutation is autosomal dominant, so a mutation in only one of the pair of chromosomes usually produces the disease. Although postmenopausal breast cancer can develop in women who carry germline mutations of these genes, cancer will develop in most of these carriers at a younger age.
Answer
E
45 A 45-year-old woman had a recent stereotactic biopsy revealing atypical ductal hyperplasia. What is the next most appropriate step in her management?
A Bilateral prophylactic mastectomies
B Tamoxifen
C Wire-localized excisional biopsy of the area
D BRCA mutation testing
E Mammography in 6 months
Ref.: 5
Comments
Certain forms of benign breast disease can be important risk factors for the eventual development of breast cancer. The classification scheme for benign breast disease usually includes nonproliferative lesions, proliferation of breast epithelium without atypia (hyperplasia), and proliferation with atypia. The relative risk for cancer in women with either atypical ductal hyperplasia or atypical lobular hyperplasia is between four and five times the risk for development of breast cancer in a control population of women. If there is a positive family history with the existence of atypical hyperplasia, the risk is increased to nearly nine times that of the general population. Tamoxifen(20 mg/day for 5 years) is considered a preventive option in women found to have atypical hyperplasia. This patient should undergo wire-localized excisional biopsy of the area because there is up to a 15% chance of having a higher-stage lesion in the area (such as DCIS) when the surrounding tissue is examined.
Answer
C
46 Which of the following statements regarding the human epidermal growth factor receptor-2 (HER-2) gene is false?
A It controls normal cell growth.
B It is amplified in 25% of breast cancers.
C Trastuzumab is an antibody against the HER-2/neu receptor.
D It is an independent predictor of poor outcome in breast cancer.
E HER-2 status is hereditary.
Ref.: 7, 16
Comments
HER-2/neu (c-erbB-2) is a protooncogene that is found on the surface of some normal cells in the body; however, it is overexpressed or amplified in 25% of all breast cancers. It is a member of the epidermal growth factor family and is a transmembrane receptor with tyrosine kinase activity. Studies have shown that HER-2/neu overexpression is found in more aggressive cancers and is a negative prognostic factor. Women with node-negative but HER-2/neu–positive breast cancer seem to have an increased risk for recurrence in comparison to node-negative HER-2/neu–negative patients. Trastuzumab is a humanized murine monoclonal antibody raised against the erb-B2 or HER-2 surface receptor. HER-2 status is not considered a hereditary trait.
Answer
E
47 Which of the following is false regarding breast reconstruction following mastectomy for breast cancer?
A The cosmetic result of immediate reconstruction is enhanced by preserving the maximum amount of breast skin during performance of the mastectomy.
B Immediate reconstruction has a detrimental effect on local recurrence rates.
C Reconstruction is often delayed in patients who might require postmastectomy radiation therapy.
D Multiple factors are considered when choosing reconstruction procedures, including age, obesity, smoking history, concomitant disease, and the patient’s psychological/emotional state.
E Autogenous tissue usually provides better symmetry than an implant.
Ref.: 12
Comments
Breast reconstruction may be performed as immediate reconstruction (same day as mastectomy) or as delayed reconstruction (months or years later). Immediate reconstruction is facilitated by preserving the maximum amount of breast skin, and it offers the advantages of combining the recovery period for both procedures and avoiding a period without reconstruction. In a recent study, 75% of reconstructions were performed immediately. Clinical trials have shown that there is no increased risk for cancer recurrence and no increased difficulty with surveillance for recurrence of breast cancer after immediate reconstruction. Reconstruction may be delayed in patients who might require postmastectomy radiation therapy and is usually delayed in patients with locally advanced cancer. Reconstructive options can be divided into two main types: those that use autogenous tissue and those that require alloplastic material. In general, autogenous tissue will usually provide better symmetry than an implant. One study showed that only 35% of transverse rectus abdominus myocutaneous (TRAM) flap reconstructions required a symmetry procedure versus 55% of implant reconstructions.
Answer
B
48 Which patient would not benefit from postmastectomy radiotherapy?
A 49-year-old with inflammatory breast cancer
B 25-year-old with 6 cm of DCIS
C 57-year-old with a T1N2 infiltrating ductal carcinoma
D 48-year-old with a 2.5-cm breast mass involving the underlying pectoral muscle
E 42-year-old with a 3.0-cm primary tumor and one lymph node positive that has extracapsular extension
Ref.: 5
Comments
Three large prospective randomized trials have addressed the role of postmastectomy irradiation, and in addition to the expected benefit of reducing local-regional recurrences, it also resulted in significant improvement in overall survival in all three studies. Postmastectomy irradiation has been found to reduce the risk for local or regional recurrence by approximately two thirds and to reduce breast cancer–specific mortality. Most centers now recommend chest wall and nodal irradiation after mastectomy for patients with multiple positive nodes (more than four positive nodes), for patients with large cancers or very aggressive histology (diffuse vascular invasion), and for extranodal extension of breast cancer. Other indications include positive surgical margins, inflammatory breast cancer, or involvement of the skin, pectoral fascia, or skeletal muscle. Radiation therapy is not indicated after mastectomy for DCIS, regardless of its size.
Answer
B
49 Which of the following patients is considered an appropriate candidate for breast-preserving therapy with lumpectomy followed by radiation therapy?
A A 40-year-old woman with a history of active scleroderma and a T1N0 infiltrating ductal carcinoma of her right breast
B A 45-year-old woman with a T1N1 infiltrating ductal carcinoma of her left breast after lumpectomy, negative surgical margins, and axillary lymph node dissection with 2 of 12 lymph nodes positive
C A 37-year-old woman with a T2N0 infiltrating ductal carcinoma of her right breast who has a history of Hodgkin disease treated with 36 Gy to a mantle field 15 years earlier
D All of the above
E None of the above
Ref.: 17, 18
Comments
The National Surgical Adjuvant Breast and Bowel Project B-06 trial demonstrated that lumpectomy followed by radiation therapy to the breast is appropriate treatment for patients with primary tumors 4 cm or less in diameter and either positive or negative axillary lymph nodes. Several other trials have confirmed these results for patients with stage I and II breast cancer. The 20-year results from the NSABP B-06 trial show equal overall survival and disease-free survival for all patients whether they were treated by breast preservation or mastectomy. However, the cohort of patients treated by lumpectomy alone without irradiation suffered a 35% recurrence rate in the ipsilateral breast. This recurrence rate is considered unacceptably high when compared with the 10% risk for ipsilateral breast recurrences in patients who underwent radiation therapy of the breast following lumpectomy. Several series have shown that patients with certain collagen vascular diseases may incur increased toxicity from radiation therapy. Although excessive complications have not been consistently shown with all types of collagen vascular disorders, severe fibrosis and soft tissue necrosis have been associated with scleroderma, thus suggesting that patients with scleroderma may be better served with a mastectomy. Patients with active systemic lupus erythematosus and rheumatoid arthritis may also be at increased risk for toxicity from radiation therapy. Mastectomy is recommended for patients who have had previous radiation therapy to the chest or to a mantle field (which includes the neck, axilla, mediastinum, and pulmonary hila) because the radiation tolerance of regional normal tissues may be exceeded and result in excessive toxicity.
Answer
B
50 A 15-year-old girl is brought to the office by her mother because of asymmetrical breast development. Physical examination reveals normal breast development on the left and a hypoplastic breast on the right, with hypoplasia of the pectoralis major muscle also seen on the right. What should the clinician explain to the mother?
A This is a normal situation in this age group since breast tissue often develops at different rates and is slightly asymmetrical during adolescence.
B This is an example of Poland syndrome.
C This is an example of Li-Fraumeni syndrome.
D This is an example of amazia.
E This is an example of fragile X syndrome.
Ref.: 19
Comments
This patient is demonstrating Poland syndrome, which is characterized by unilateral hypoplasia of the breast, pectoral muscles, and chest wall. Li-Fraumeni syndrome is one of the inherited breast cancer syndromes in which there is an increased incidence of breast cancer, soft tissue sarcoma and osteosarcoma, brain tumors, adrenocortical cancer, and leukemias in the same family. Nearly 30% of the tumors in these families occur before the age of 15. Amaziarefers to a condition in which the nipple is present but the breast mound is absent.
Answer
B
51 A 13-year-old girl is referred to a breast surgeon for breast asymmetry secondary to a rapidly growing right breast mass. Physical examination reveals an 8-cm central right breast mass. She underwent menarche 1 year ago. Breast cancer was diagnosed in her mother at age 38. What is the appropriate next step?
A Mastectomy
B Incisional biopsy
C Mammogram
D Ultrasound
E Reassurance to the patient and her mother that this is normal breast development
Ref.: 7
Comments
See Question 52.
Answer
D
52 Regarding the patient in the Question 51, ultrasound reveals an 8-cm hypoechoic solid mass with rounded edges. What is the next appropriate step in the management of this patient?
A Excisional biopsy
B Mastectomy
C Cyst aspiration
D Bilateral mastectomies
E Reassurance to the patient and mother
Ref.: 7
Comments
This young woman most likely has a juvenile fibroadenoma. Fibroadenoma may be regarded as a generic term and refers to any benign, confined tumor of the breast that has a mixture of glandular and mesenchymal elements; juvenile fibroadenoma is considered a variant. These lesions tend to occur in women in the younger age range and are characterized by increased cellularity of stroma or epithelium. Juvenile fibroadenomas are notable for their rapid growth and large size and tend to occur around the time of menarche. They often have a common ductal pattern of epithelial hyperplasia and defining stromal hypercellularity. The initial imaging modality for a young woman is ultrasound because it is accurate in evaluating the dense breast tissue common in younger women, involves no radiation exposure, and is essentially painless. A rounded hypoechoic solid mass on ultrasound is indicative of fibroadenoma, and excisional biopsy would be considered appropriate treatment at this time.
Answer
A
53 Which statement is false regarding radial scars?
A Usually detected as a stellate lesion on mammography
B Extensive elastosis is common
C May be associated with or contain atypical ductal hyperplasia or DCIS
D Increases the risk for the future development of breast cancer by 40%
E Benign proliferative disease of the breast
Ref.: 20
Comments
Radial scars are benign breast lesions of uncertain etiology and behavior. They have a characteristic low-power stellate architecture with cystically dilated glands encircling the periphery. The mostly acellular core is composed of connective tissue and elastin surrounded by radiating bands of compressed ducts and lobules that demonstrate dual myoepithelial and epithelial layers. Proliferative epithelial lesions, including sclerosing adenosis, hyperplasia, and papillomas, are often seen within radial scars. One large review study found that radial scars do not confer an increased risk for subsequent breast cancer over that of other proliferative lesions, although there is a slightly increased association between radial scars and atypical hyperplasia. The growth pattern in radial scars can resemble a malignancy and is difficult to distinguish from invasive carcinoma on mammography, which prompts biopsy of these lesions.
Answer
D
54 A 45-year-old woman has an abnormal diagnostic mammogram revealing a cluster of indeterminate microcalcifications in the upper outer quadrant of her left breast. Physical examination reveals normal findings. The patient denies any risk factors for breast cancer. Which of the following is most appropriate for initial management?
A Stereotactic-guided core needle biopsy
B Ultrasound-guided core needle biopsy
C Reassurance and continuation of yearly mammography
D Excisional biopsy
E Repeat mammography of the left breast in 6 months
Ref.: 13
Comments
One of the goals of modern breast medicine is to reduce the number of unnecessary open surgical breast biopsies for benign lesions. Imaging-guided percutaneous needle biopsy is the diagnostic procedure of choice for imaging-detected breast abnormalities. It should be readily available to all patients with imaging-detected lesions. The presence of indeterminate microcalcifications is a suspicious finding on mammography that warrants a tissue diagnosis; therefore, reassurance or close follow-up is not an appropriate management option. Ultrasound is the preferred biopsy guidance method for sonographically visible lesions, but this lesion was found on mammography, and therefore stereotactic guidance would most likely be the initial choice for biopsy.
Answer
A
55 A 57-year-old woman undergoes imaging-guided biopsy of a 1.5-cm spiculated, centrally dense mass. Pathologic review shows benign breast parenchyma. Which of the following is the most appropriate recommendation at this point?
A Routine screening mammography in 1 year
B Additional imaging with contrast-enhanced MRI
C Short-term follow-up in 4 to 6 months
D Wire-localized excisional biopsy
E Tamoxifen
Ref.: 19
Comments
When mammographic changes are highly suspicious for malignancy but a negative core biopsy is obtained, these results must be viewed with caution because the possibility of sampling error must always be considered. Definitive wide excision with wire localization in such circumstances would then be warranted. The reasons for the initial core biopsy in such suspicious cases are multiple and include the value of having a tissue diagnosis (rather than just a “suspicion”) when discussing diagnosis and management options with the patient. Negative MRI findings would not preclude additional biopsy of this mammographically suspicious lesion.
Answer
D
56 A 47-year-old woman undergoes a modified radical mastectomy for a T2N2 infiltrating ductal carcinoma. She arrives at her first postoperative visit complaining of hypoesthesia of the upper posteromedial aspect of the ipsilateral arm. What might explain this finding?
A Lymphatic fibrosis
B Medial pectoral pedicle injury
C Second intercostal brachial cutaneous nerve injury
D Axillary vein thrombosis
E Thoracodorsal pedicle injury
Ref.: 19
Comments
A number of neurovascular structures are identified and dissected during axillary dissection that are at risk for injury. The axilla is rich in lymphatic vessels draining the ipsilateral arm. Some of these lymphatics are disrupted during axillary dissection, but continued fibrosis of the remaining lymphatics, especially in cases in which the dissected axilla has been irradiated, may lead to progressive lymphedema of the arm, which can begin years after therapy. The possibility of unsightly and disabling lymphedema occasionally developing has led to a generally more conservative surgical approach toward axillary dissection for breast cancer in recent years. The medial pectoral pedicle contains the principal motor nerve and partial blood supply to the pectoralis major muscle. Injury leads to atrophy but not ischemia because the blood supply to this muscle is derived from many different sources. The second intercostal brachial cutaneous nerve provides sensation to the upper lateral chest wall and medial and posterior aspect of the upper part of the arm. It passes transversely across the axilla about 1 to 2 cm caudal to the axillary vein. In the past, it was routinely sectioned to allow cleaner en bloc removal of the axillary contents, but many surgeons now choose to preserve it in cases in which it is not in close proximity to clinically suspicious lymph nodes. The axillary vein can be narrowed or ligated as a result of surgical error during the procedure or can undergo acute spontaneous thrombosis during the immediate postoperative period. Because collateral channels have not had a chance to develop, the resulting swelling of the ipsilateral arm is usually acute and painful. The thoracodorsal pedicle contains the motor nerve and the principal artery and vein serving the latissimus dorsi muscle. Injury to the nerve leads to atrophy, but this is rarely clinically significant, except in athletes. Loss of the vascular pedicle distal to its branch to the serratus muscle, however, would lead to ischemic loss of the latissimus dorsi myocutaneous rotation flap, one of the principal sources of autologous tissue for breast reconstruction and for closure of soft tissue deficits of the chest wall. The long thoracic nerve is also at risk for injury during axillary surgery; such injury can cause loss of function of the serratus anterior muscle and in turn lead to winging of the scapula.
Answer
C
57 What is the incidence of lymphedema after axillary node dissection (levels I and II)?
A 5%
B 10%
C 20%
D 40%
E 50%
Ref.: 7
Comments
The incidence of lymphedema after axillary node dissection ranges from 15% to 30%, depending on the definition used. The probability of lymphedema increases with greater dissection and level of nodes removed, the tumor burden in the axilla, the presence of lymphedema before surgery, and whether radiation is applied to the field after surgery. With the advent of sentinel lymph node biopsy, the rate of lymphedema has been shown to be much lower, in the range of 2% to 4%.
Answer
C
58 Radiation delivered to the breast after right lumpectomy and sentinel lymph node biopsy for a 1.2-cm node-negative infiltrating ductal carcinoma is likely to be associated with which of the following?
A Decreased risk for systemic recurrence
B Can be used in lieu of chemotherapy in early-stage breast cancers
C Increased risk for lymphoma
D Decreased risk for local recurrence
E Cardiac toxicity
Ref.: 7
Comments
The addition of breast irradiation after breast conservation has been shown in multiple randomized trials to decrease the incidence of local tumor recurrence but is considered controversial in terms of survival benefit. Radiation is used for local control, and chemotherapy is a modality for systemic control; the decision for chemotherapy is made independently and based on the presence of tumor factors and risk for distant disease. Lymphoma is not associated with breast irradiation. The risk for cardiac toxicity in right-sided lesions with modern techniques of radiation therapy planning and dosimetry is very low.
Answer
D
59 For which patient described below is an aromatase inhibitor, such as anastrozole (Arimidex) or letrozole (Femara), considered to be useful?
A A 57-year-old woman with T1N0 ER-positive breast cancer
B A 35-year-old woman with LCIS
C A 65-year-old woman with T2N1, ER-negative breast cancer
D A 42-year-old woman with DCIS
E A 45-year-old woman who is a known carrier of the BRCA mutation
Ref.: 7, 19
Comments
Aromatase inhibitors are useful only in the postmenopausal setting for women with invasive cancers. In postmenopausal women, the ovaries stop producing estrogen, but low levels of estrogen remain because aromatase converts other steroid hormones into estrogen in the peripheral fat. The ATAC trial (Arimidex, tamoxifen, alone or in combination) showed that in postmenopausal women with invasive breast cancer, taking anastrozole led to a lower recurrence rate, a lower chance for the development of a new primary, and less toxicity than in women taking tamoxifen. A subset analysis of this trial showed that the advantage of anastrozole was seen only in women with steroid receptor–positive breast cancer. Tamoxifen may be indicated for chemoprevention in high-risk patients, such as those with LCIS or DCIS or those carrying a BRCA mutation. Aromatase inhibitors, however, are not currently approved for chemoprevention.
Answer
A
60 What additional treatment should a 42-year-old patient with a 2-cm focus of ER-positive DCIS transected at the margin by lumpectomy receive?
A Radiation therapy alone
B Tamoxifen alone
C Surgical reexcision alone
D Surgical reexcision and tamoxifen alone
E Surgical reexcision, radiation therapy, and tamoxifen
Ref.: 7, 19
Comments
If ductal carcinoma has been transected at the margin of resection, its rate of recurrence is unacceptably high in both the noninvasive and invasive forms. Reexcision to clear margins is the standard of care. Subsequent radiation therapy significantly reduces local recurrence and is recommended for all but the smallest of tumors. The addition of tamoxifen has been shown to further decrease the incidence of recurrent DCIS and new invasive breast cancer. Recent studies have shown that this benefit is best seen in women with ER-positive DCIS.
Answer
E
61 Which of the following is associated with the appearance of invasive lobular carcinoma on mammography?
A Discrete bilateral masses
B Partially cystic appearance
C Indistinct mass with poorly defined borders
D Masses with microcalcifications
E Branching pleomorphic microcalcifications
Ref.: 5
Comments
When compared with invasive ductal carcinoma, invasive lobular carcinoma tends to be more indistinct and difficult to visualize on mammograms. The extent of the tumor is often underestimated on the mammogram and may be more accurately appreciated by ultrasound imaging or magnetic resonance imaging. Nonetheless, recurrence and survival rates for invasive lobular carcinoma are equivalent to those for ductal carcinoma, stage for stage.
Answer
C
62 In which population is the incidence of BRCA mutations highest?
A Ashkenazi Jews
B Patients with a history of radiation therapy for Hodgkin disease
C Patients with a first-degree relative with breast cancer
D A woman with a Gail score of 2.3%
E A woman with a prior diagnosis of uterine cancer
Ref.: 7
Comments
The BRCA mutation rate is highest in Ashkenazi Jews and ranges from 1% to 3%. The incidence of breast cancer in those who underwent mantel irradiation for Hodgkin disease is five times that of the general population. A person with a first-degree relative with postmenopausal breast cancer has a relative risk 1.8 times that of the general population. Ovarian cancer increases the risk for breast cancer in a woman, but uterine cancer has not been linked to breast cancer.
Answer
A
63 What is the approximate false-negative rate for sentinel lymph node biopsy?
A 1%
B 8%
C 15%
D 20%
E 25%
Ref.: 7, 19
Comments
The sentinel lymph node biopsy technique has a learning curve of approximately 30 cases before proficiency is attained. In experienced hands, the false-negative rate ranges from 4% to 12%. The use of tracer blue dye versus technetium-labeled sulfur colloid, or both, has not been shown to affect the detection rate or false-negative rate if the surgeon is proficient. Isosulfan blue dye, however, is associated with a small incidence of anaphylactoid reactions.
Answer
B
64 In which patient should MRI be used as an adjunct to mammography for breast cancer screening purposes?
A A 27-year-old woman in whose mother breast cancer was diagnosed at age 52
B A 52-year-old woman with dense breasts
C A 72-year-old woman with a history of DCIS
D A 31-year-old woman whose sister carries the BRCA mutation but has declined genetic testing for herself
E A 55-year-old woman who received radiation treatments at age 50 for uterine cancer
Ref.: 21
Comments
Magnetic resonance imaging uses magnetic fields to produce detailed cross-sectional images of tissue structures and provides very good soft tissue contrast. The ACS has recommendations for breast MRI screening as an adjunct to mammography based on certain levels of evidence. The ACS recommends annual MRI screening (based on evidence from nonrandomized screening trials and observational studies) for patients with the BRCA mutation, those with first-degree relatives who are BRCA carriers but are themselves untested, and those with a lifetime risk of 20% to 25% or greater for the development of breast cancer, as defined by BRCAPRO or other models that are largely dependent on family history. The ACS recommends annual MRI screening (based on expert consensus opinion and evidence of lifetime risk for breast cancer) for those with irradiation of the chest between 10 and 30 years of age, patients and their first-degree relatives with Li-Fraumeni syndrome, and patients and their first-degree relatives with Cowden disease and Bannayan-Riley-Ruvalcaba syndrome. There is insufficient evidence to recommend for or against MRI screening in the following subgroups: those with a lifetime risk of 15% to 20%, as defined by BRCAPRO or other models that are largely dependent on family history, those with LCIS or atypical lobular hyperplasia, patients with atypical ductal hyperplasia, women with heterogeneously or extremely dense breasts on mammography, and women with a personal history of breast cancer, including DCIS. The ACS recommends against MRI screening for women with less than a 15% lifetime risk for breast cancer.
Answer
D
65 Which of the following has typically been associated with breast pain?
A Breast cancer
B LCIS
C DCIS
D Sclerosing adenosis
E Breast cysts
Ref.: 5, 7
Comments
Although breast pain may be the most common initial breast symptom, it is rarely associated with carcinoma. Normal ovarian hormonal influences on breast glandular elements frequently produce cyclic mastalgia. Occasionally, a simple cyst may cause noncyclic breast pain, and aspiration of the cyst ends the evaluation. Frequently, lifestyle and dietary changes result in improvement of mastalgia. Decreasing caffeine intake and the use of bras with better support are the first steps in the management of breast pain. Medications such as danazol, primrose oil, and nonsteroidal antiinflammatory drugs have been shown to occasionally be effective in refractory cases. In many cases, patients report a lessening of the pain after being reassured that the pain is not associated with cancer.
Answer
E
66 An ultrasound image of a patient’s breast reveals a 2-cm simple cyst. Aspiration yields clear straw-colored fluid, and there is complete resolution on postprocedure ultrasound imaging. What should the clinician’s next step be?
A Order repeat ultrasound imaging in 3 months.
B Have the fluid sent to the laboratory for Hemoccult testing, cytologic studies, and assessment for tumor markers.
C Perform wire-localized excision of the cavity.
D Prescribe antibiotics for the patient.
E Advise the patient to continue with routine clinical breast examinations and mammograms.
Ref.: 19
Comments
A simple cyst that completely resolves after aspiration of straw-colored fluid needs no further diagnostic or surgical evaluation. Routine follow-up with clinical examination and scheduled mammograms is indicated. If the cyst recurs, especially in the postmenopausal setting, surgical excision should be considered.
Answer
E
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