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

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

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

Which of the following breast lesions are noninvasive malignancies?



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

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




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


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



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

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

1.About 25% of the lymphatic drainage of the breast courses to the internal mammary nodes
2.Nerves within the axillary fat pad include the intercostal brachial nerve, the long thoracic nerve, and thoracodorsal nerve
3.Fascial bands projecting through the breast to the skin form a supporting framework known as Coopers ligaments
4.The ductal system of the breast from the alveoli to the skin are lined with columnar epithelium
Answer: b, c
The breast abuts against the fascia of the pectoralis major and serratus anterior muscles.
Projections of the fascia course through the breast to the skin, forming a supporting
framework of the breast parenchyma. These fascial bands, called suspensory ligaments
of Cooper, are better developed in the upper breast. The structure of the breast can be
divided into lobular and ductal elements. The lobule is the functional unit of the breast.
Within a lobule, the terminal elongated tubular ducts are referred to as alveoli. Ten to
one hundred alveoli coalesce to form a larger duct which defines a lobular unit. The
lobular ducts join to form progressively larger ducts and ultimately an excretory duct.
The alveolar ducts, lobular ducts, and excretory ducts are all lined with either cuboidal
or columnar epithelium. Eventually, 10-20 excretory ducts, each dilate into a short
excretory sinus (lined with squamous epithelium) just beneath the areola. Excretory
ducts then course perpendicular to exit through the nipple.

The lymphatic anatomy of the breast is of interest to the surgeon because of the tendency of breast cancer to
involve the regional lymph nodes. Studies using radioactive tracers demonstrate at least 97% of lymphatic flow
from the breast is into the axilla; the remainder courses into the internal mammary nodes. These studies also
show that lymph flowing into the internal mammary gland chain is not restricted in origin to the medial half and
sub-areolar region of the breast, as was thought, but can originate in any quadrant of the breast. In the axilla,
lymphatic vessels terminate in the lymph nodes embedded within the axillary fat pad. Also within the axillary fat
pad are the intercostal brachial nerves (a sensory nerve supply in the under arm), the long thoracic nerve (a motor
nerve to the serratus anterior and subscapularis muscles) and the thoracodorsal nerve (a motor nerve to the
latissimus dorsi adjacent to its accompanying arteries and veins).
Which of the following statement (s) is/are true concerning the recurrence of breast cancer?

1.The majority of patients recur within five years of diagnosis
2.More than 70% of breast cancer recurrence involve distant metastases
3.Pulmonary metastases are the most common initial site of distant recurrence
4.The local recurrence rate following breast-conserving procedures varies from 10% to 40% whether or not radiation was used
5.Recurrent disease will be seen in at least 35% of node-negative patients undergoing appropriate primary breast therapy
Answer: a, b, d

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

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

1.Up to 50% of cancers detected mammographically are not palpable
2.One third of palpable breast cancers are not detected by mammography
3.The sensitivity of mammography increases with age
4.The American Cancer Society currently recommends routine screening mammography
beginning at age 40
Only about 10% of nonpalpable lesions detection mammographically are found to be malignant at
biopsy
Answer: a, c, d

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

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

1.The most common organism which would expect to be
cultured is Staphylococcus aureus
2.Open surgical drainage is likely indicated
3.Breast-feeding absolutely should be discontinued
4.If the inflammatory process does not completely respond, a
biopsy may be indicated
Answer: a, b, d

Infection complicates breast-feeding in fewer than 1:100 women, but these lactational
infections still account for 80% of all breast infections. Presumably, gaining access via
the skin of the irritated nipple of the nursing woman, Staphylococcus aureus is by far the
most common pathogen in this setting. Many breast infections begin as cellulitis, without
abscess formation. When an actual abscess is suspected, percutaneous aspiration can
establish the diagnosis and allow for bacterial culture and sensitivity testing. Open
surgical drainage is the most prudent and effective treatment. Although women may
choose to cease breast feeding, there is no absolute indication for this. When mastitis or
breast infection is suspected clinically, the possibility of an inflammatory carcinoma must
also be entertained. Any inflammatory process that does not respond completely and
promptly to antibiotics or drainage should be subjected to biopsy to rule out cancer.
Which of the following statement(s) is/are true concerning the surgical staging of breast cancer?

1.All biopsy specimens should be transported to pathology in formalin within 24 hours of the procedure
2.Removal of only level I axillary lymph nodes may understage breast cancer in up to one-fourth of patients
3.Level III axillary lymph nodes should be removed in all axillary lymph node dissections
4.A clinically negative axilla will be found to have histologically positive metastasis in approximately one-third
of patients
Answer: b, d

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

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

1.If the patient has received adjuvant therapy, her response is likely to be better
2.If the patient is ER-positive, hormonal therapy should be the first line of treatment
3.The response to chemotherapy will likely be dose-dependent
4.Combination chemotherapy will likely work better in this patient than a woman who is post-
menopausal
Answer: b, c, d

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

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

1.Mammography will play an important role in diagnosing the lesion
2.Ultrasonography is often useful in the differential diagnosis of this lesion
3.The mass should always be excised
The lesion should be considered pre-malignant
Answer: b

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

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


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


Answer: c

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

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

1.The tumor is most commonly seen in post-menopausal women
2.Total mastectomy is necessary for all patients with this diagnosis
3.Axillary lymph node dissection is not necessary for malignant cystosarcoma
phyllodes
4.Most patients with the malignant variant of cystosarcoma phyllodes die of
metastatic disease
Answer: c

Cystosarcoma phyllodes is a tumor arising in the mesenchymal tissue of the breast. The tumors
usually present as a painless breast mass. Phyllodes tumor is most commonly encountered in
women age 3040 years of age but can occur at any age, even before puberty. The differentiation
of a benign from a malignant phyllodes tumor may be difficult. About one-fourth of all phyllodes
tumors are histologically malignant, but only a fraction of these patients actually develop metastatic
disease. The optimum treatment for benign or malignant phyllodes tumor is wide excision with a
margin of normal breast tissue. The margin must be histologically free of involvement because even
benign lesions can recur after incomplete excision. If this can be done leaving an adequate
cosmetic appearance, mastectomy is not necessary. Total mastectomy is reserved for large lesions
in small-breasted women or recurrences after previous local excision that is not amenable to repeat
local excision. Axillary lymph node dissection is not performed in the absence of biopsy-proven
nodal involvement, even for malignant phyllodes tumors, because axillary metastases are
uncommon.

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

1.Adjuvant tamoxifen in post-menopausal, node-positive, ER-positive women is equivalent to
cytotoxic chemotherapy
2.Tamoxifen clearly improves survival in all hormonal receptor-positive patients
3.CMF is associated with improved overall survival in both pre-menopausal and post-
menopausal node-positive patients
4.There is no evidence to suggest a role for chemotherapy in node-negative patients
Answer: a

Adjuvant tamoxifen leads to a prolonged disease-free interval in post-menopausal ER-positive women with
histologically positive nodes and in pre-menopausal and post-menopausal ER-positive women with negative
nodes. Because of similar results and, because tamoxifen is generally less toxic than chemotherapy, this
treatment is the treatment of choice for post-menopausal, node-positive, ER-positive women. CMF
(cyclophosphamide, methotrexate, and 5-fluorouracil) is associated with both a longer disease-free survival and
overall survival time in pre-menopausal patients with positive lymph nodes. In post-menopausal women with
positive nodes, there is an improved disease-free survival, but there is no significant difference in overall survival.
Several trials of adjuvant chemotherapy with CMF or related regimens have been conducted in node-negative
patients. The early results of all of these trials have been similar: disease-free survival is definitely improved with
adjuvant chemotherapy. These studies are definitely not mature enough to draw definitive conclusions regarding
overall survival. Therefore, the National Cancer Institute has recommended the use of adjuvant chemotherapy for
all patients with tumors large enough to have hormonal receptor levels measured.
A 33-year-old woman is referred with nipple discharge. Which of the following statement(s) is/are true concerning
her diagnosis and management?

1.Bilateral galactorrhea is suggestive of an underlying endocrinopathy
2.Brownish discharge is usually suggestive of old blood and is worrisome for an underlying breast cancer
3.Expressible bloody nipple discharge should be evaluated with a ductogram
4.Milky breast discharge would not be expected one year after discontinuation of breast feeding
Answer: a, c

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

Which of the following statement(s) is/are associated with gynecomastia?

If the disease is unilateral, it is unlikely drug-related
The standard surgical treatment is subcutaneous mastectomy
The presence of gynecomastia is often associated with the subsequent development of breast cancer
A formal endocrine evaluation is indicated in most patients with gynecomastia
Answer: b

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


6. Axillary lymph node dissection is routinely used for all of the following conditions except:
A. 2-cm. pure comedo-type intraductal carcinoma.
B. 1-cm. infiltrating lobular carcinoma.
C. 8-mm. infiltrating ductal carcinoma.
D. A pure medullary cancer in the upper inner quadrant.
Answer: A
DISCUSSION: Intraductal carcinoma is carcinoma in situ and does not metastasize to regional or distant sites.
Lymph node dissection is not routinely required for a pure in situ cancer of the breast. In contrast, all of the other
cancers listed above (infiltrating lobular, infiltrating ductal, and medullary carcinoma) are invasive malignancies
that are capable of nodal and distant metastasis. Lymph node dissection is commonly recommended for these
invasive malignancies. Intraductal lesions that have grown larger than 5 cm. are more apt to have become focally
invasive. Since this invasive component might be missed histologically, many surgeons advocate selective use of
axillary node dissection for large intraductal lesions, particularly high-grade tumors such as the comedo variant.
However, a purely intraductal 2-cm. cancer would most likely be treated without performing node dissection.

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



A. Recurrence of cancer in the ipsilateral breast.
B. Shorter survival time.
C. Regional nodal recurrence.
D. Greater chance of breast cancer mortality.
Answer: A
DISCUSSION: Retrospective reviews and prospective surgical trials agree that omission
of breast radiation after wide excision leads to a higher rate of ipsilateral breast
recurrence. However, survival and the risk of distant disease are not altered in patients
treated by excision alone, within the follow-up time of the studies and given their
inherent power to detect differences in outcome. Regional node metastasis is not
affected by the choice of mastectomy versus wide excision and radiation
Which of the following statement(s) is/are true concerning the surgical staging of breast cancer?






1.All biopsy specimens should be transported to pathology in formalin within 24 hours of the
procedure
2.Removal of only level I axillary lymph nodes may understage breast cancer in up to one-
fourth of patients
3.Level III axillary lymph nodes should be removed in all axillary lymph node dissections
A clinically negative axilla will be found to have histologically positive metastasis in approximately
one-third of patients
Answer: b, d

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