Breast cancer

1. Breast cancer
Yonas Ademe
Nov, 2017
1

2. Epidemiology
• Breast cancer is the most common site-specific cancer in
women and is the leading cause of death from cancer for
women aged 20 to 59 years
• Breast cancer burden has well-defined variations by
geography, regional lifestyle, and racial or ethnic
background
– In general, both breast cancer incidence and mortality are
relatively lower among the female populations of Asia and
Africa, relatively underdeveloped nations, and nations that
have not adopted the Westernized reproductive and dietary
patterns
• Women begin childbearing at young ages and have multiple full-term
pregnancies followed by prolonged lactation
2

3. Cont.
• The average lifetime risk of breast cancer for
newborn U.S. females is 12%
• The longer a woman lives without cancer the
lower her risk of developing breast cancer
3

4. Risk factors
• Hormonal
– Increased exposure to estrogen is associated with an
increased risk for developing breast cancer, whereas
reducing exposure is thought to be protective
• Factors that increase the number of menstrual cycles such as
early menarche, nulliparity, and late menopause, are
associated with increased risk
• Moderate levels of exercise, a longer lactation period, and
factors that decrease the total number of menstrual cycles, are
protective
– The terminal differentiation of breast epithelium associated with a
full-term pregnancy is also protective
» Older age at first live birth is associated with an increased risk
of breast cancer
4

5. Cont.
• Non-hormonal
– Radiation exposure
– Alcohol consumption
• Alcohol is known to increase serum levels of estradiol
– High fat diet
• Long-term consumption of foods with a high fat content
increases serum estrogen levels
– Obesity
• Associated with a long-term increase in estrogen exposure
– Because the major source of estrogen in postmenopausal women is
the conversion of androstenedione to estrone by adipose tissue
5

6. Cont.
• General
– Old age
– Female
– White race
– Family history
• Hormonal
– Early menarche
– Late menopause
– Nulliparity
– Old age at first live birth
• Non-hormonal
– High fat diet
– Obesity
– Alcohol
– Radiation
6

7. Cont.
7

8. Genetics
• Up to 5% of breast cancers are caused by
inheritance of germline mutations such as BRCA1
and BRCA2, which are inherited in an autosomal
dominant fashion with varying degrees of
penetrance
• Both BRCA1 and BRCA2 function as tumor
suppressor genes, and for each gene, loss of both
alleles is required for the initiation of cancer
8

9. Cont.
• Risk management strategies for BRCA1 and BRCA2
mutation carriers include the following:
– Risk-reducing mastectomy and reconstruction
• Reduces the cancer risk but mastectomy does not remove all
breast tissue and women continue to be at risk because a
germline mutation is present in any remaining breast tissue
– Risk-reducing salpingo-oophorectomy
• Should be done between the ages of 35 and 40 years at the
completion of childbearing
– Chemoprevention
– Intensive surveillance for breast and ovarian cancer
9

10. Breast cancer screening
• Breast self-examination
– Age ≥ 20 years
– Monthly
• Clinical breast examination
– Women in their 20s and 30s
• At least every 3 years
– Women aged ≥40 y
• Annually
• Imaging
– Mammography
• Should be started at age 40 years
– Ultrasonography
• It can be used for breast cancer screening in women with dense breasts
– MRI
• Family history, BRCA mutation carriers, those individuals who have a family
member with a BRCA mutation, and individuals who received radiation to the
chest between the ages of 10 to 30 years
10

11. Breast cancer prevention
• Chemoprevention
– Tamoxifen, a selective estrogen receptor modulator, was the first
drug shown to reduce the incidence of breast cancer in healthy
women
– Indications
• Gail relative risk of 1.66% or higher
• Age 35 to 59
• Age of 60 or women with a diagnosis of LCIS or atypical ductal or lobular
hyperplasia
– Risks
• VTE
• Endometrial cancer
• Risk-reducing Surgery (bilateral prophylactic mastectomy)
– For carriers of a breast cancer susceptibility gene (BRCA) mutation
11

12. Natural history
• Primary breast cancer
– More than 80% of breast cancers show productive fibrosis
that involves the epithelial and stromal tissues
– With growth of the cancer and invasion of the surrounding
breast tissues, the accompanying desmoplastic response
entraps and shortens Cooper’s suspensory ligaments to
produce a characteristic skin retraction
– Localized edema (peaud’orange) develops when drainage of
lymph fluid from the skin is disrupted
– With continued growth, cancer cells invade the skin, and
eventually ulceration occurs
– As new areas of skin are invaded, small satellite nodules
appear near the primary ulceration
12

13. Cont.
• Cont.
– The size of the primary breast cancer correlates with
disease-free and overall survival, but there is a close
association between cancer size and axillary lymph
node involvement
– In general, up to 20% of breast cancer recurrences
are localregional, >60% are distant, and 20% are
both local-regional and distant
13

14. Cont.
• Axillary lymph node metastases
– As the size of the primary breast cancer increases, some
cancer cells are shed into cellular spaces and transported via
the lymphatic network of the breast to the regional lymph
nodes, especially the axillary lymph nodes
– Lymph nodes that contain metastatic cancer are at first ill-
defined and soft but become firm or hard with continued
growth of the metastatic cancer
– Eventually the lymph nodes adhere to each other and form a
conglomerate mass
– Cancer cells may grow through the lymph node capsule and
fix to contiguous structures in the axilla, including the chest
wall
14

15. Cont.
• Cont.
– Typically, axillary lymph nodes are involved
sequentially from the low (level I) to the central
(level II) to the apical (level III) lymph node groups
– Approximately 95% of the women who die of breast
cancer have distant metastases, and traditionally
the most important prognostic correlate of disease-
free and overall survival was axillary lymph node
status
• Women with node-negative disease had less than a 30%
risk of recurrence, compared with as much as a 75% risk
for women with node-positive disease
15

16. Cont.
• Distant Metastases
– At approximately the 20th cell doubling, breast cancers
acquire their own blood supply (neovascularization)
– Thereafter, cancer cells may be shed directly into the
systemic venous blood to seed the pulmonary
circulation via the axillary and intercostal veins or the
vertebral column via Batson’s plexus of veins
• Common sites of involvement, in order of frequency, are bone,
lung, pleura, soft tissues, and liver
– Brain metastases are less frequent overall
– Successful implantation of metastatic foci from breast
cancer predictably occurs after the primary cancer
exceeds 0.5 cm in diameter, which corresponds to the
twenty-seventh cell doubling
16

17. Cont.
• Cont.
– For 10 years after initial treatment, distant metastases
are the most common cause of death in breast cancer
patients
– Although 60% of the women who develop distant
metastases will do so within 60 months of treatment,
metastases may become evident as late as 20 to 30
years after treatment of the primary cancer
– Patients with estrogen receptor negative breast cancers
are proportionately more likely to develop recurrence in
the first 3 to 5 years
17

18. Histopathology
18

19. Carcinoma in situ
• Lobular Carcinoma In Situ (LCIS)
– It originates from the terminal duct lobular units
and develops only in the female breast
– It is characterized by distention and distortion of
the terminal duct lobular units by cells which are
large but maintain a normal nuclear: cytoplasmic
ratio
– It may be observed in breast tissues that contain
microcalcifications, but the calcifications associated
with LCIS typically occur in adjacent tissues
(neighborhood calcification)
19

20. Cont.
• Cont.
– Occurs more frequently in white women
– Invasive breast cancer develops in 25% to 35%
• Up to 65% of subsequent invasive cancers are ductal, not
lobular, in origin
– LCIS is regarded as a marker of increased risk for invasive breast
cancer rather than as an anatomic precursor
– Individuals should be counseled regarding their risk of
developing breast cancer and appropriate risk reduction
strategies, including observation with screening,
chemoprevention, and risk-reducing bilateral
mastectomy
20

21. Cont.
• Ductal Carcinoma In Situ (DCIS)
– Although DCIS is predominantly seen in the female
breast, it accounts for 5% of male breast cancers
– Histologically, DCIS is characterized by a proliferation of
the epithelium that lines the minor ducts, resulting in
papillary growths within the duct lumina
– Calcium deposition occurs in the areas of necrosis and is
a common feature seen on mammography
– Invasive breast cancer develops in 25-70%
– The invasive cancers are observed in the ipsilateral
breast, usually in the same quadrant as the DCIS that
was originally detected, which suggests that DCIS is an
anatomic precursor of invasive ductal carcinoma
21

22. Cont.
• Cont.
– Classification of breast DCIS
22

23. LCIS Vs. DCIS
• Multicentricity refers to
the occurrence of a second
breast cancer outside the
breast quadrant of the
primary cancer (or at least
4 cm away)
• Multifocality refers to the
occurrence of a second
cancer within the same
breast quadrant as the
primary cancer (or within 4
cm of it)
23

24. Invasive Breast Carcinoma
• Invasive breast cancers have been described as lobular
or ductal in origin
• Foote and Stewart classification
– Paget’s disease of the nipple
– Invasive ductal carcinoma (80%)
• Adenocarcinoma with productive fibrosis (scirrhous, simplex, NST)
– Medullary carcinoma (4%)
– Mucinous (colloid) carcinoma (2%)
– Papillary carcinoma (2%)
– Tubular carcinoma (2%)
– Invasive lobular carcinoma (10%)
– Rare cancers (adenoid cystic, squamous cell, apocrine)
24

25. Cont.
• Invasive ductal carcinoma of the breast
– It presents with macroscopic or microscopic axillary
lymph node metastases in up to 25% of screen-
detected cases and up to 60% of symptomatic cases
– It occurs most frequently in perimenopausal or
postmenopausal women in the fifth to sixth decades
of life as a solitary, firm mass
– 75% of ductal cancers show estrogen receptor
expression
25

26. Cont.
• Paget’s disease of the nipple
– It frequently presents as a chronic, eczematous eruption of
the nipple, which may be subtle but may progress to an
ulcerated, weeping lesion
– It usually is associated with extensive DCIS and may be
associated with an invasive cancer
– A palpable mass may or may not be present
– Pathognomonic of this cancer is the presence of large, pale,
vacuolated cells (Paget cells) in the rete pegs of the
epithelium
– Surgical therapy for Paget’s disease may involve lumpectomy
or mastectomy, depending on the extent of involvement of
the nipple-areolar complex and the presence of DCIS or
invasive cancer in the underlying breast parenchyma
26

27. Diagnosis
27

28. Clinical features
• Symptoms
– In~30% of cases, the woman discovers a lump in her breast
– Other less frequent presenting signs and symptoms of breast
cancer include:
• Breast enlargement or asymmetry
• Nipple changes, retraction, or discharge
• Ulceration or erythema of the skin of the breast
• An axillary mass
• Musculoskeletal discomfort
• Breast pain usually is associated with benign disease
– Up to 50% of women presenting with breast complaints have
no physical signs of breast pathology
28

29. Cont.
• Physical examination
– Inspection
• Done with her arms by her side, with her arms straight up
in the air, and with her hands on her hips (with and
without pectoral muscle contraction)
• Symmetry, size, and shape of the breast are recorded, as
well as any evidence of edema (peaud’orange), nipple or
skin retraction, or erythema
• With the arms extended forward and in a sitting position,
the woman leans forward to accentuate any skin
retraction
29

30. Cont.
• Cont.
– Palpation
• Palpate the breasts, making certain to examine all
quadrants of the breast from the sternum laterally to the
latissimus dorsi muscle and from the clavicle inferiorly to
the upper rectus sheath
– With the patient in supine position
• Palpate lymph nodes in the axilla, supraclavicular and
parasternal areas
– Sitting position
30

31. Imaging
• Mammography
– There is no increased breast cancer risk associated
with the radiation dose delivered with screening
mammography
– Views
• Craniocaudal view
• Mediolateral oblique view
• 90-degree lateral view (used in diagnostic
mammography)
• Spot compression views (used in diagnostic
mammography)
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32. Cont.
• Cont.
– Specific mammographic features that suggest a
diagnosis of breast cancer include:
• A solid mass with or without stellate features
• Asymmetric thickening of breast tissues
• Clustered microcalcification
32

33. Cont.
• Ultrasonography
– Second only to mammography in frequency of use for breast
imaging
– Advantages
• Resolving equivocal mammographic findings
• Demonstrating the echogenic qualities of specific solid abnormalities
• Defining cystic masses
• Imaging the regional lymph nodes
– Size larger than 1 cm, cortical thickening, change in shape of the node to
more circular appearance, absence of a fatty hilum and hypoechoic internal
echoes
• Guiding FNAB
– Disadvantages
• It does not reliably detect lesions that are ≤1 cm in diameter
• Operator dependent 33

34. Cont.
• MRI
– Highly sensitive and specific
• However, in the circumstance of negative findings on both
mammography and physical examination, the probability
of a breast cancer being diagnosed by MRI is extremely
low
– It can also detect additional tumors in the index
breast (multifocal or multicentric disease)
34

35. Breast biopsy
• FNAB or core needle biopsy
– Image-guided for non-palpable lesions
– Core-needle permits the analysis of breast tissue
architecture and allows the pathologist to
determine whether invasive cancer is present
– Added advantages include a low complication rate,
minimal scarring, and a lower cost compared with
excisional breast biopsy
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36. Staging
36

37. Staging
• The clinical stage of breast cancer is determined
primarily through physical examination of the skin,
breast tissue, and regional lymph nodes (axillary,
supraclavicular, and internal mammary)
– However, clinical determination of axillary lymph node
metastases has an accuracy of only 33%
• US is more sensitive
• FNA or core biopsy of sonographically indeterminate or
suspicious lymph nodes can provide a more definitive
diagnosis
37

38. TNM staging
• Tis: carcinoma in situ
• T1: tumor ≤2 cm in greatest dimension
– T1mi: tumor ≤1 mm in greatest dimension
– T1a: tumor >1 mm but ≤5 mm in greatest dimension
– T1b: tumor >5 mm but ≤10 mm in greatest dimension
– T1c: tumor >10 mm but ≤20 mm in greatest dimension
• T2: tumor >2 cm but ≤5 cm in greatest dimension
• T3: tumor >5 cm in greatest dimension
• T4: tumor of any size with direct extension to the
chest wall and/or to the skin (ulceration or skin
nodules
38

39. Cont.
• N1: metastases to movable ipsilateral level I, II axillary lymph
node(s)
• N2
– Metastases in ipsilateral level I, II axillary lymph nodes that are
clinically fixed or matted OR
– In clinically detected ipsilateral internal mammary nodes in the
absence of clinically evident axillary lymph node metastases
• N3
– Metastasis in ipsilateral infraclavicular (level III axillary) lymph
node(s) with or without level I, II axillary lymph node involvement
– In clinically detected ipsilateral internal mammary lymph node(s)
with clinically evident level I, II axillary lymph node metastases
– Metastases in ipsilateral supraclavicular lymph node(s) with or
without axillary or internal mammary lymph node involvement
39

40. Cont.
• M0: no clinical or radiographic evidence of
distant metastases
• M1: distant detectable metastases as determined
by classic clinical and radiographic means and/or
histologically proven larger than 0.2 mm
40

41. Cont.
41

42. Treatment
42

43. Introduction
• Once a diagnosis of breast cancer is made, the type
of therapy offered to a breast cancer patient is
determined by the stage of the disease, the
biologic subtype and the general health status of
the individual
• Options
– Surgery
– Radiotherapy
– Chemotherapy
– Hormonal therapy
43

44. Steroid receptor
• Patients with hormone receptor-positive
tumors survive two to three times longer after a
diagnosis of metastatic disease than do patients
with hormone receptor-negative tumors
– Tumors positive for estrogen or progesterone
receptors have a higher response rate to endocrine
therapy than tumors that do not express estrogen
or progesterone receptors
44

45. Growth factor receptor
• Overexpression of EGFR in breast cancer
correlates with estrogen receptor-negative
status and with p53 overexpression
– Similarly, increased immunohistochemical
membrane staining for the HER-2/neu growth
factor receptor in breast cancer is associated with
mutated p53, Ki-67 overexpression, and estrogen
receptor–negative status
• HER-2/neu is a member of the EGFR family of growth
factor receptors
45

46. Male breast cancer
46

47. Introduction
• Fewer than 1% of all breast cancers occur in men
• It has a peak incidence in the sixth decade of life
• It is preceded by gynecomastia in 20% of men
• It is associated with radiation exposure, estrogen
therapy, testicular feminizing syndromes, and
Klinefelter’s syndrome (XXY)
47

48. Cont.
• DCIS makes up <15% of male breast cancer,
whereas infiltrating ductal carcinoma makes up
>85%
• Male breast cancer is staged in the same way as
female breast cancer, and stage by stage, men with
breast cancer have the same survival rate as
women
• Overall, men do worse because of the more
advanced stage of their cancer (stage II, III or IV) at
the time of diagnosis
48

49. Management
• A firm, non-tender mass in the male breast
requires investigation
• The treatment of male breast cancer is surgical,
with the most common procedure being a
modified radical mastectomy
49

50. Cont.
• Adjuvant radiation therapy is appropriate in cases in
which there is a high risk for local-regional recurrence
• Approximately 80% of male breast cancers are hormone
receptor positive, and adjuvant tamoxifen is considered
• Systemic chemotherapy is considered for men with
hormone receptor-negative cancers and for men with
large primary tumors, multiple positive nodes, and
locally advanced disease
50

51. End!
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