Transcript breast cancer - Doç. Dr. Gökhan SÖĞÜTLÜ | Malatya

BREAST CANCER
DR. GÖKHAN SÖĞÜTLÜ
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Breast cancer is either noninvasive(in situ) or
invasive(spreading)
Ductal carcinoma in situ
Lobular carcinoma in situ
LC in situ is a marker for an incresed risk of
invasive cancer in both breasts ( same breast
%18 and other breast %14 after 20 years)
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Invasive cancer occurs when cancer cells
spread beyond the basement mebrane.
Infiltrating ductal ca
Infiltrating lobular ca
They comprises between 70% and 80% ; 10%
and 15% of all breast cancers respectively.
The typical carcinoma of the breast (80 to 85
percent) is a scirrhous adenocarcinom with
prodictive fibrosis that orginates in the
ductules and invades the parenchyma
RİSK FACTORS
Age
 More than 80 % of breast cancer cases occur
in women over 50 .
 Cancer in women younger than 30 is very rare,
accounting for only 1.5% of all breast cancer
cases.
 A woman’s chances for breast cancer are 1/8 in
their whole life.
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Ethnicity
North America and Northen Europe people high risk
(industrial countries), Asian and African people low risk (nonindustrial countries)
 Genetic factors and family history
*20-30% of all women with breast cancer have a family history
(familial)
*5-10% of all women with breast cancer have hereditary
*This often appears in young women under age 50
*In such families, some members may also have developed
ovarian cancer as well.
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HEREDITARY
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Genes are as follows;
-BRCA1 or BRCA2 are now believed to be responsible for
30% to 50% of hereditary breast cancer, ovarian cancer or
both in families with a history of these cancers.
- About 90% of BRCA1 carriers will develop breast cancer in
whole lifetime.
-These mutations can be passed down to the doughter by
either mother or the father.
-These are present in only about 0.1 of the population.
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Other defective genes that contribute to breast
cancer including BRCA3, p53,CDKN2A
A mutation in a gene located on chromosome
10 called PTEN gene results in a disorder called
Cowden syndrome, which is associated with a
higher risk of breast cancer.
RİSK FACTORS(con.)
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Over-exposure to estrogen
Because growth of breast tissue is highly
sensitive to estrogens, the more a women is
exposed to estrogen over her lifetime,the higher
the risk for breast cancer.
For women in whom menopause occurs after
the age of 45 the risk of developing the disease
is twice as high as for those whose menopause
started before age 45.
 Artificially surgical menopause appears to be
protective for breast cancer. Protection is
lifelong and removal of endogenous estrogen
dramatially reduces breast cancer risk.
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The earlier the surgical menopause
(oophorectomy at age thirty five or younger),
the lower the risk.
 Early menarche also increases the risk
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Pregnanncy and abortion
 Infertility and nulliparity are associated with a
higher probability.
 With decreasing age at the time of first
pregnancy,the risk decreases proportionately.
 Women impregnated before 18 who have a
full-term pregnancy have a breast cancer risk
1/3 that for women pregnant after 35.
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Women,first full-term pregnancy after the age
30, have an even greater risk for breast cancer
than do nullipars.
 Women who have had abortions have risk but
this is very small.
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Oral contraception
 New low-dose OCs do not appear to pose this
risk (more research is needed)
 HRT (hormone replacement theraphy)
 Estrogen use by premenopausal and
postmenopausal women for HRT may slightly
increase the risk of breast cancer.
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The risk is said to be accentuated in women with
preexisting benign disease of the breast.
 Prolonged use increases the risk
 Interestingly, some studies suggest that in
women with a history of breast cancer, HRT
does not increase risk for recurrence
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Risk factors (con.)
Physical characteristics
 Breast cancer risk is directly correlated with
relative weight; the risk for obese women is 1.5
to 2 times higher than for nonobese women.
 This relative risk is restricted to postmenopausal
individuals.
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There have been conflicting reports of a link
between increased height and breast cancer risk.
 One study found no association.
 Other studies, however, found that taller adult
height predicted a greater risk, possibly due to
the higher estrogen levels associated with greater
bone growth.
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Multipl primary neoplasms
 Women with a history of primary breast cancer
have a risk 3 to 4 times higher for primary
cancer in the contrlateral breast.
 History of previous ovarian and endometrial
carcinoma.
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Environmental factors
 Exposure to estrogen –like industrial chemicals
(xenoestrogens). They are found in pesticides and other
common industrial products.
 Radiation exposure
Children receiving high dose radiation theraphy face an
increased risk for breast cancer in adulthood.
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Mental health
 A 2000 study suggested that women who had a
history of major depression were four times as
likely to develop breast cancer.
 Stress was not found as a risk factor.
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Insulin-like growth factor
Insulin-like growth factor 1 is an important
growth hormone during development in the
womb and childhood. High concentrations have
now been linked to cancers, including
premenapousal breast cancer.
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Alcohol
Risk is increased 1.5 fold when drunk regularly.
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Benign breast disease
Hyperplasia without AH 1.5-2 fold
 AH 4-5 fold
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How can the risk of breast cancer
be lowered?
Regular exercise (by modulating estrogen)
 Dietary factors
 Fats
Although some studies have found an association
between high-fat intake and breast cancer, the most
recent data suggest that fat from any source plays at
most insignificant role in incresing the risk for breast
cancer.
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Vitamins and chemicals in fruits and vegetables
Many fresh fruits and vegetables contain
chemicals that may be cancer fighter.
Cabbage, broccoli, cauliflower, turnip, kale
Apples, onion, green tea (contains
polyphenols)
Tomatos(lycopen)
Avocado, bananas, fruits, orange juice (folic
acid)
Iron
High iron stores have been associated with a
higher risk for breast cancer
 Protein
Fish may offer some protection
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Breast feeding
Evidence on protection from breast feeding is
weakly positive.
symptoms
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Hard lump
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50% of such masses are found in the upper outer
quarter of the breast.
The nipple may be retracted or scaly
Sometimes, the skin of the breast is dimpled like
the skin of an orange. Skin ulceration may
occur.
In some cases there is a bloody or clear
discharge from the nipple
Axillary mass
Diagnosis
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Early detection of breast cancer significantly
reduces the risk of death
20-49 ages
physical examination by a health
professional every 1 to 2 years.
50 and over
should be examined annualy
Women should perform self examination every
month.
Mammogram
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Mammograms are very effective low-radiation
screening
They are not foolproof, however
In general, they still miss up to 25% of cancers (which
can sometimes be caught on a physical
examination)*****
Screening mammogram every 12 to 33 months
significantly reduced mortality, at least in women over
55 (a 33% reduction in mortality for woman after
screening mammogaphy).
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There are, however, a number of issues as to
who should screen and when to screen.
For women between ages 50 and 69. Evidence
suggest that annual mammograms save lives in
this age group (per 2 years in our country).
40-50 should be tested every 1 to 2 years until
age 50.
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Overall, diagnostic mammography has a 90%
sensitivity, 10% false positive rate and 7% false
negative rate.
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Ultrasonography
New ultrasound techniques can detect tumors
smaller than 1 centimeter.
 However, ultrasound is a time-consuming procedure,
and remains less efficient than mammogram
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Other imaging techniques
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Scintomammography
Dopler ultrasonography
Breast MR
Biopsy
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A definitive diagnosis of breast cancer can be
made only by a biopsy.
When a lump can be felt and is suspicious for
cancer on mammography;
 FNAB
 Excisional
biopsy
 İncisional biopsy
 Core biopsy
 Radioguided biopsy (for occult lumps)
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A wire localization biopsy may be performed if
mammography detects abnormalities but there is
no lump (microcalcifications)
A new vacuum-assisted device may be useful for
some biopsies.
Prognostic factors
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A number of factors are used to determine
outlook;
Size and lymh nodes status
 Nuclear grade
 Age
 The location of the tumor and far it has spread
(tumors that develop toward the outside of the
breast tend to be less serious than those that occur
more toward the middle of the breast).
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Whether the tumor is hormone receptor-positive or
negative
Breast cancer cells may contain receptors, or binding
sites, for hormones like estrogen or progesterone.
Hormone receptor positive cells grow more slowly
than recptor negative cells.
Women have a better prognosis if their tumors are
receptor-positive.
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The influence of BRCA genes
The relevance of the BRCA1 or BRCA2 mutations
to survival is controversial
Women with these genetic mutations do have a
greater risk for a new cancer to develop.
Poor differentiation (for BRCA-1)
Well differentiation (for BRCA-2)
High bilateralism
Early onset of age
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Tumor markers
HER-2 is part of the epidermal growth factor
receptor family and is becoming an important
marker in breast cancer.
The precence of HER-2 may suggest agresive
cancer.
Angiogenesis factors (such as vascular endothelial
growth factor)
P53 gene. P53 is a tumor suppessant gene.
CA 15-3, c-erb-B-2, cathepsin-D, telomerase, bFGF, Ki-67… are others.
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Rate of cell division. Mitotic index (MI) is a
measurement of the rate at which cells divide; the
higher the MI, the more agresive the cancer.
Staging
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Histopatologic types are as follows:
Carcinoma
Ductal
• İntraductal (in situ)
• Invasive
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Scirrhous (adenoca. with productive fibrosis)
Medullary
Mucinous (colloid)
Tubuler
Papillary
Inflammatory
Lobular
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In situ
Invasive
Nipple
• Paget’s disease
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Sarcoma
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Relaviley rare carcinomas
Infiltrating ductal carcinoma with
prodictive fibrosis (scirrhous)
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The 80 percent frequency of adenocarcinoma of the
breast (ductal carcinoma)
The tumor characteristically possesses a poorly defined
border, firm, immobile.
It’s cut surfaces show a central stellate configuration
with white or yellow streaks extending into surrounding
breast tissues.
Medullary carcinoma
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4%
Orginates in large ductus
Grossly, the tumor is characterised by its soft,
hemorrhagic bulky presentation
Commonly, the lesion is positioned deep within the
breast and mobile.
Diagnosis of this lesion connotes a better 5-year
survival than pure invasive ductal or lobular carcinoma
Mucinous (colloid) carc.
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This adenocarcinoma of ductal origin
constitutes approximately 2% of all breast
cancers and typically presents as a bulky,
mucinous (colloid) tumor that is largely confined
to the elderly population.
5- year survival better than ductal and lobular
carcinomas (5-year survival rates is reported as
about 73%)
Tubuler carcinoma
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This lesion is a well-differantiated variant of
breast carcinoma with an incidence of
approximately 2 percent.
Most commonly, is diagnosed in the
perimenapousal or early menopausal population.
Long term survival is perfect
Papillary carcinoma
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Papillary cacinoma accounts for less than 2
percent of all breast carcinomas and generally
presents in the 7. decade.
Typically, papillary cancer is small and rarely
attains sizes greater than 2 to 3 cm in diameter.
Papillary carcinoma is more indolent, slowly
progressive disease than the common
adenocarcinoma
Best 5 and 10 year survival rates
Lobular carcinoma
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These carcinomas originate in terminal ductules of the lobule
and posses characteristic features that distinguish them from
lesions of the larger, lactiferous ducts.
The noninvasive form is lobular carcinoma in situ (LCIS).
Constitutes approximately 10 percent of breast cancers
At presentation, ILC varies from clinically unapparent cancers to
those that replace entire breast with a poorly defined mass
These lesions have a high propensity for bilaterality, multicentrity
and multifocality.
Paget’s disease of the nipple
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Approximately 2%
It is almost always associated with an
underlaying extensive intraductal (DCIS) or
invasive carcinoma
It presents as an encrusted, scaly, hyperemic, and
enlarged tumor that occupies the surface of the
nipple-areola complex
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Symptoms include tenderness, itching, burning,
and intermittent hemorrhage.
Intraductal adenocarcinomas often involve the
epidermis of the nipple and areola by
intraepithelial dissemination.
Physical findings in the nipple-areola complex
precede the identification of a palpabl mass in
the subareolar area.
In general, better prognosis than the majority
of lesions, because the nipp-areol cahanges
promote early consulatation
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Differantiation from pagetoid intraepithelial
melanoma is based on S-100 antigen
immunostaining in melanoma and CEA
immunostaining in Paget’s disease.
Surgical theraphy may involve lumpectomy or
MRM.
Sarcomas
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Rarely tumours
These tumors include fibromatosis,
fibrosarcoma, liposarcoma, leimyosarcoma,
angiosarcoma…
Inflammatory carcinoma
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1.5 to 3%
Clincal features of erythema, peau d’orange, and skin
ridging (at least 50% of whole brast) with or without
the presence of a palpabl mass are evident.
Typically the skin over the lesion is warm, diffusely
scaly, and indurated with ridging
It may present with the charecteristics of a cellulits.
The tumor mass may be diffuse or nondefinable
Diagnosis is established by biosy of skin, subcutaneous
tissue, and parenchyma
This disease progresses rapidly and prognosis is poor.
TNM
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Tx
Tis
T1
T2
T3
T4a
T4b
T4c
T4d
No evidence of primary tumor
Carcinoma in situ
Tumor 2cm or <
2 to 5 cm
T> 5cm
extension to chest wall
edema (including peau d’orange), ulceration
of skin, satellite nodules
T4a + T4b
Inflammatory carcinoma
Peau d’orange:
 With progressive diffuse skin infiltration in the
subdermal lymphatic plexus. There is extensive edema
of the skin, reffered to as peau d’orange
Skin retraction:
 Characteristic involvement of Cooper’s ligaments
Regional lymh nodes
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N0
N1
N2
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N3
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no regional lymh node met.
Movable ipsilateral axillary l.nod.
Fixed ipsilateral axillary lymph n. or
İnternal mammary lymh nodes
-İpsilateral supraclavicular l.n.
-Fixed ipsilateral axillary lymph n. and
İnternal mammary lymh nodes
-İpsilateral infraclavicular l.n.
Pathologic classification (pN)
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pNX: Regional lymph nodes cannot be assessed (e.g., not removed for pathologic study or previously removed)
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pN0: No regional lymph node metastasis histologically, and no additional examination for isolated tumor cells
(ITC)
[Note: ITCs are defined as single tumor cells or small cell clusters not larger than 0.2 mm, usually detected
only by immunohistochemical (IHC) or molecular methods but that may be verified on hematoloxylin & eosin
(H&E) stains. ITCs do not usually show evidence of malignant activity, e.g., proliferation or stromal reaction.]
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pN0(I-): No regional lymph node metastasis histologically, negative IHC
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pN0(I+): No regional lymph node metastasis histologically, positive IHC, and no IHC cluster larger than 0.2
mm
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pN0(mol-): No regional lymph node metastasis histologically, and negative molecular findings (RT-PCR)*
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pN0(mol+): No regionally lymph node metastasis histologically, and positive molecular findings (RT-PCR)*
* [Note: RT-PCR: reverse transcriptase-polymerase chain reaction.]
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pN1: Metastasis in 1-3 axillary lymph nodes, and/or in internal mammary nodes with microscopic
disease detected by SLN dissection but not clinically apparent**
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pN1mi: Micrometastasis (larger than 0.2 mm but not larger than 2.0 mm)
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pN1a: Metastasis in one to three axillary lymph nodes
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pN1b: Metastasis in internal mammary nodes with microscopic disease detected by SLN dissection but
not clinically apparent**
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pN1c: Metastasis in one to three axillary lymph nodes and in internal mammary lymph nodes with
microscopic disease detected by SLN dissection but not clinically apparent.** (If associated with more
than three positive axillary lymph nodes, the internal mammary nodes are classified as pN3b to reflect
increased tumor burden.)
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pN2: Metastasis in 4-9 axillary lymph nodes, or in clinically
apparent ** internal mammary lymph nodes in the absence of
axillary lymph node metastasis to ipsilateral axillary lymph
node(s) fixed to each other or to other structures
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pN2a: Metastasis in four to nine axillary lymph nodes (at least one tumor
deposit larger than 2.0 mm)
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pN2b: Metastasis in clinically apparent* internal mammary lymph nodes
in the absence of axillary lymph node metastasis
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pN3: Metastasis in 10 or more axillary lymph nodes, or in infraclavicular lymph nodes,
or in clinically apparent* ipsilateral internal mammary lymph node(s) in the presence of
1 or more positive axillary lymph node(s); or, in more than three axillary lymph nodes
with clinically negative microscopic metastasis in internal mammary lymph nodes; or,
in ipsilateral supraclavicular lymph nodes
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pN3a: Metastasis in 10 or more axillary lymph nodes (at least 1 tumor deposit larger than 2.0
mm); or, metastasis to the infraclavicular lymph nodes
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pN3b: Metastasis in clinically apparent* ipsilateral internal mammary lymph nodes in the
presence of one or more positive axillary lymph node(s); or, in more than three axillary lymph
nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel
lymph node dissection but not clinically apparent**
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pN3c: Metastasis in ipsilateral supraclavicular lymph nodes
Distant metastasis
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M0
M1
Treatment
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Surgery, radiation or drug theraphy.
Breast cancer treatment are defined as local or
systemic
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Local: Surgery and radiation.
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Surgery is usually the standart initial treatment
Systemic: Drug treatment
Stage 0
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Also called noninvasive carcinoma or carcinoma
in situ.
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Lobular carcinoma in situ
Careful monitoring with or without preventive use
of tamoxifen
In selected cases, consideration of removal of both
breasts
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Ductal carcinoma in situ
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Mastectomy (previously was the commonly recommended
treatment)
Breast-sparing surgery followed by radiotheraphy is
reasonable treatment for many women
Use of tamoxifen or other SERMs after surgery and
radiation to prevent recurrence in selected patients
Stage I and II
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Breast sparing surgery (lumpectomy,
quadranectomy…) followed by external beam
radiation theraphy
Modified radical mastectomy
Adjuvant theraphy
Combination chemotheraphy
 Hormonal theraphy
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StageIII
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Mastectomy usually with radiotheraphy and
systemic treatment (combination
chemotheraphy, hormonal theraphy or both)
Neoadjuvat chemotheraphy followed by surgery
+ adjuvant chemotheraphy is recommended.
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Five-year survival rates for individuals with breast
cancer who receive appropriate treatment are
approximately:
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100% for stage 0
100% for stage I
92% for stage IIA
81% for stage IIB
67% for stage IIIA
54% for stage IIIB
20% for stage IV