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Breast cancer
Reham abdulmonem, MD
Epidemiology
Breast cancer is the most frequently diagnosed cancer in
women in United States excluding the skin.
A total of 211,300 cases and 39,800 deaths per year.
Second leading cause of deaths in women.
Worlwide 1 million cases are seen annually.
Primarily due to increased utilization of screening
mammography, breast cancer incidence rates increased
rapidly in the 1980s.
Table 1 Ten Most Common Cancers among
Saudis, 2004 (All Ages
Anatomy of breast
It extends from 2nd to 6th rib •
Covered by pectoralis muscle that is •
inserted in the acromian process of the
scapula
Anatomy
• Medial and Lateral Borders of breast tissue
typically the sternum & mid axillary line.
• Cranial and Caudal borders typically the 2nd
anterior rib & 6th anterior rib.
• Primary lymphatic drainage is to axillary, internal
mammary and SCV nodes.
Anatomy of the Breast
Regional Lymph Nodes:
1. Axillary
2. Supraclavicular
3. Internal mammary
Anatomy LN drainage
1. Axillary (ipsilateral): •
a. Level I (low axilla): lymph nodes lateral to •
the lateral border of pec minor.
b. Level II (midaxilla): lymph nodes between •
the medial & lateral borders of pec minor
c. Level III (apical axilla): lymph nodes medial •
to the medial margin of the pec minor muscle
2. Internal mammary (ipsilateral): along the •
edge of the sternum in the endothoracic
fascia
Axillary Lymph nodes
Breast cancer
►Incidence:
• The most common cancer among women
• Accounts for 30% of all female cancers
• Increases with age (> 50 years, 75% in postmenopausal)
► Risk Factors:
• Hereditary: +ve family history in 15%
• Tumor suppressor genes (e.g. BRACA-1, BRACA-2)
• Hormones: endogenous exposure to estrogen and progesterone
• Early menarche,
• Late menopause,
• Delayed childbirth, and
• Postmenopausal obesity
Risk Factors-Age
Age plays a major role in breast cancer risk.In •
women under 30, breast cancer is extremely
uncommon.
The incidence of breast cancer in women aged 35
to 39 was 59 per 100,000; however, in women 55
to 59, the incidence was 296 per 100,000.
Breast cancer increases steeply with age until •
menopause. After menopause, although the
incidence continues to increase, the rate of increase
decreases to approximately one-sixth of that seen in
the premenopausal period.
•
Risk Factors-Familial
The majority of women diagnosed with breast
•
cancer do not have a family member with the
disease.
Only 5% to 10% have a true hereditary •
predisposition to breast cancer.
Overall, the risk of developing breast cancer is •
increased 1.5- to 3.0-fold if a woman has a
mother or sister with breast cancer.
Risk Factors-hereditary
The possibility of a mutation in either
•
BRCA1 or BRCA2 should be considered
when breast cancer is diagnosed at a young
age (i.e., less than 45 to 55), when multiple
relatives are affected, when there is a history
of other cancers in the family (particularly
ovarian cancer), or any combination of these
factors.
THESE ARE GENETIC FACTORS •
Breast Cancer
Pathology
► Adenocarcinoma: 90%
• Ductal: 80%
• Lobular: 10%
► Special types: <10%
• Papillary carcinoma
• Mucinous carcinoma
• Medullary carcinoma
► Inflammatory carcinoma: 1%
• Poorest prognosis
Pathology
OTHERS •
DCIS ------in ducts •
LCIS--------in lobules •
DCIS-clinical presentation
An abnormal mammographic report of •
clustered microcalcifications is currently
the most common presentation of DCIS.
DCIS can also present as a mass or •
pathologic nipple discharge, or can be
identified as an incidental finding in a
breast biopsy.
DCIS
Mastectomy is a curative treatment for •
98% to 99%.
DCIS-conservative ttt B17
818 women were randomized to excision alone •
or excision plus 5000 cGy of irradiation to the
breast.
At 90 months of follow-up,The 8-year incidence •
of invasive recurrence was significantly reduced
from 13.4% to 3.9% by irradiation, and the
incidence of recurrent DCIS was also
significantly reduced from 13.4% to 8.2%.
DCIS Tamoxifen NSABP-24
1804 patients with DCIS treated by •
lumpectomy and RT were randomized to
tamoxifen (20 mg daily) or placebo for 5 years.
Follow-up of 62 months,the risk of ipsilateral •
recurrence of any type (invasive or noninvasive)
or of new contralateral breast cancers was
reduced from 13.0% to 8.8% at 5 years,
LCIS
LCIS is not detectable on macroscopic •
examination and is always an incidental
microscopic finding in breast tissue removed for
another reason
80% to 90% of cases of LCIS occurring in •
premenopausal women
LCIS is frequently noted to be bilateral., •
LCIS is associated with an increased risk
•
for the development of breast carcinoma that
is approximately seven to ten times equal in
both breasts.
LCIS ttt
management option for the woman with LCIS is •
careful observation,
The use of tamoxifen in women electing
•
observation only.
Wide surgical excision and histologically •
negative margins are not needed when careful
follow-up is chosen given that LCIS is known to
be a multifocal lesion. Similarly, RT has no role
in the management of LCIS. assumes.
T classification
The pathologic tumor size for classification (T) is •
a measurement of only the invasive
component.
Microinvasion is the extension of cancer cells •
beyond the basement membrane into the
adjacent tissues with no focus more than 0.1 cm
in greatest dimension.
Multiple Simultaneous Ipsilateral Primary •
Carcinomas,the largest primary carcinoma to
classify T.
T staging
T1-------TUMOUR LESS THAN 2CM •
T2-------TUMOUR FROM 2-5CM •
T3--------TUMOUR MORE THAN 5CM •
T4--------TUMOUR INVADES ADJACENT •
STRUCTURES AS SKIN ,CHEST WALL
Staging I & II
III A , B
III C , IV
N1
pN1a micro •
<0.2 cm •
pN1mi <0.2cm>0.2mm •
pN1b macro>0.2 cm •
pN1bi 1-3 LN –
any>0.2cm,all<2.0cm
pN1bii>4LN –
pN1biii ECE <2 cm –
pN1biv >2cm –
pN1:1-3 and /or IM ( mic)
detected by
lymphscintigraphy
pN1a 1-3 LN –
pN1bIM (mic) –
pN1c both a+b –
•
N2
pN2 ipsilateral axillary fixed –
to one another
pN2:4-9 axillary •
nodes or clinically
apparent IM in
absence of axillary
nodes
pN2a 4-9 axillary –
nodes
pN2bclinically –
apparent IM
N3
pN3 ipsilateral internal
mammary
•
pN3a:>10 axillary LN or •
infraclav
pN3b Or Clinically •
apparent IM in the
presence of positive
axillary nodes
pN3b Or >3 axillary LN •
in the presence of
microscopic diseasein IM
pN3c Or Ipsilateral •
Supraclav
M---METASTASIS
MO----NO METS •
M1-----METS POSITIVE •
Prognosis
Survival By Stage
Stage
5-Yr survival (%)
10-Yr survival (%)
0
99
95
I
97
88
II
83
66
III
54
36
IV
16
7
Breast Cancer
Diagnosis
► Symptoms & Signs:
• Breast lump: solitary, unilateral, hard, irregular, nontender
• Nipple discharge: bloody and unilateral ( >50 years)
• Others:
•Local: skin changes
•Regional: axillary lymphadenopathy
•Distant: metastases
► Breast Imaging:
• Mammography: detects 85%
• Ultrasonography: women under 30 year
• MRI: if mammography and ultrasound are normal
► Breast Biopsy: FNA cytology or excisional
► Staging Procedures: for invasive breast cancer
Mammography
Signs of malignancy:
• Clustered microcalcification
• Irregular or speculated mass
• solid mass with ill-defined borders
• enlarging solid mass
• development of density when compared with
a previous mammogram
A BIOPSY IS MANDATORY
FROM A DISCRETE MASS
EVEN IF MAMMOGRAPHY
IS FREE OR LACK OF
GROWTH OVER TIME
HOW
DIAGNOSTIC PROCEDURES
(A)
FNAC: SHOULD BE DONE BEFORE
SURGERY SO AS TO HELP THE
SURGEON DEFINE THE SURGICAL
PROCEDURE. BUT STILL IF
NEGATIVE , EXCISION BIOPSY IS
MANDATORY
(B)
Open biopsy
• UNLESS THE LESION IS BIG, EXCISION
OF THE WHOLE MASS WITH SAFTEY
MARGINS SHOULD BE DONE
(C)
IF NO MASSES ARE FELT
• A SMALL MASS IS ONLY DETECTED BY
MAMMOGRAPHY, THEN WIRE LOCALISATION
IS DONE BY RADIOLOGIST AND SOMETIMES
INJECTION OF METHYLENE BLUE .
•
In all cases a follow up mammography should be done after 2 months to
be sure that the mass was excised
On the pathological
specimen
ER&PR
Ploidy
Huer2/ne
Cathepsin D
Metastatic work-up
• chest x-ray
• Abd. And pelvic ultrasound
• bone scan if lymph nodes are detected, T3 or
sites of severe bone tenderness
Management
SURGERY
Types: •
Conservative
lumpectomy •
quadrantectomy •
wide local excision •
Modified radical mastectomy •
Palliative mastectomy
eg.simple •
mastectomy
Types of breast
Surgery
Definition
Lumpectomy
Removal of the primary tumor with a margin
Total mastectomy
Removal of the breast but not the axillary
contents
Modified radical
mastectomy
Removal of the breast up to pectoralis minor
muscle plus an axillary level I/II dissection
Radical
mastectomy
Skin-sparing
mastectomy
Removal of the parenchyma breast tissue
and pectoralis major muscle plus an axillary
level I/II dissection
Total or modified radical mastectomy with
preservation of a significant component of the
native skin of the breast
SURGICAL TREATMENT
Conservative surgery
Axillary dissection + P/O radiation is a must
Clinical indications
Absolute contra-indications:
•
mass less than 4 cm
•
age above 35 yrs
•
•
•
•
•
•
multicenteric tumors
inadequate safety margins
Diffuse micro – calcifications
Pregnancy 1st, 2nd trimenster
Previous radiotherapy
Active SLE,Scleroderma
Breast-reconstructive Technique
• Saline
implant
•
Myocutanou
s
flap
(
TRAM ) flap
or
a
latissimus
dorsi flap.
Surgery-MRM
Involve complete removal of the breast, the •
underlying pectoral fascia, and some of the
axillary nodes.sparing the muscles
The switch to modified radical mastectomy •
occurred when it became recognized that
treatment failure after breast cancer surgery
usually is caused by the systemic dissemination
of cancer cells before surgery,
rather than an
inadequate operative procedure.
Axillary dissection
Sentinel LN
Definition
The first node in the
lymphatic basin that
recieves primary
lymphatic flow.
Indications
• T1-T2
• LN –VE
• No multifocality
• No prior neoadjuvant cth
Tech
Tc99. Sulfur colloid,
methylene blue ,or both.
peritumoral,
IMH, PCR
St gallen…
-ve axillary SNB is now
accepted as allowing
avoidance of axillary
dissection
Reconstruction
The incidence of local failure in patients
•
undergoing breast reconstruction appears
to be comparable with patients treated
by mastectomy alone.
Detection of local recurrence is not •
altered by immediate reconstruction.
Indications for PORT
Postoperative RT may be given to improve •
local control or to improve survival.
Patients with four or more positive lymph
nodes should receive postoperative RT
Primary tumor >4 cm •
Radiotherapy
Post BCT
•
In >4 positive axillary LN , RT is given
to breast + SCV
( NCCN category 1 ).
•
In 1-3 positive axillary LN, RT is given
to breast, SCV radiation is
controversial
( NCCN category 2B ).
•
If negative LN, RT is given to the
breast
.
MANAGEMENT OF
EARLY BREAST CANCER
BCT vs Mastectomy
• NSABP BO6 ; randomised 1406 pts between mastectomy
and BCT. 12y OAS=62% in both arms ,distant mets 49% vs
50% .other trials give same results. 25ys update concluded
that 2nd malignancy was 2% vs 3% respectively.
• NSABP BO6 randomised 1137 pts (maximum tumor size
4cm ,l.n +ve in 37% of pts) between BCT with and without
RT ; local failure was 11% vs 37%, DM was 40% vs 44%. 25
years update local rec was 14% vs 39% with significant
increase in OAS.
• Conclusion:if T1-2 N0-1 CONSEVATIVE SURGERY +XRT
=MRM+XRT
Mastectomy + RT in
T1, T2 N0
NO however
• Retrospective analysis of 1790 patients (T1, T2 N0)
performed mastectomy with PORT compared to
patients performed mastectomy alone
• Proved absolute improvement of OS by 2.5 : 6.9% in
patients received RT
• Prospective trials are needed to prove this hypothesis
and to estimate the benefit.
CHEMOTHERAPY
GIVEN IN ALL CASES IF THE TUMOUR •
IS MORE THAN 1CM
Types: •
Taxane based •
Anthracycline based •
Type of chemotherapy
•
•
•
•
FAC/FEC
AC
CMF (not in Her2/neu +)
TAXAINES ( SINGLE AGENT OR TAC)
more important 4-9 LN +
Treatment policy
LNMinimal risk
TAM
NONE
LN+
Average risk
ER-
CTH
ER+
ER+
CTH+TAM
TAM
TAM+goserlin
ER-
Chemotherapy effect EBCTCG
metaanalysis ON 50000 PATIENTS
SHOWED IMPROVEMENT OF OAS
AGE
LN -ve
LN +ve
50Y
7%
11%
50-70Y
2%
3%
Hormonal treatment
Mode of action
Decrease tumour growth by
• decreasing E
• Blocking the receptors
Modulate TGFα, and β or IGF1
Modulation of signaling protein (protein
kinase c ‘’PKC’’)and other cell components
involved in apoptosis.
hypothalamus
Adrenal gland
GnRH
ACTH
Pitutary gland
androstendione
FSH, LH
Aromatase
ovary
estradiol
estrogen
Tumour proliferation
and growth
Tumour cell
E receptor
nucleus
Commonly used
• Oopherectomy in premenopausal by (surgical
ovariectomy, medical by Gn RH analogue and RT) so
decreasing estrogen
• Selective ER modulator SERMs anti estrogens
(Tamoxifene, tormefene, raloxifene, idoxifene, and
arzoxifene) by occupying estrogen receptor
BREAST
CANCER
PATIENTS
BREAST
CANCER
PATIENTS
ER+
50 : 60%
ONLY
RESPOND
TO HORMONAL
TTT
.
30% ONLY
RESPOND
TO
HORMONAL
TTT
WHY
Parameters reflecting hormone sensitivity:
HR+ve, G., site of mets.,HER2 concentration
Hormonal ttt lines
2 nd line
1 st line
aromatase inhibitor
premenopausal
postmenopausal
Duration of hormonal ttt
Gn RH analogue
Tam
EBCTCG metanalysis
RT oophrectomy
now
of randomised trials
surg. ovarectomy
aromatase inhibitor
5y >2y >1y
tam
NSABP B14 2001
combinations
no benefit from
to 10 y
duration
Combinations
HORMONAL + RADIOTHERAPY
Sequential not concurrent due to pulmonary fibrosis (old theory)
HORMONAL + CHEMOTHERAPY
now concurrent…….as hormonal ttt
•
•
•
interfere with lipid memberane so diffusion of CT
alter Ca++ channels so diffusion of CT
high incidence of thromboembolic diseases
Management of advanced breast
cancer
T3-4N+VE OR –VE •
COMBINATION OF TRAETMENT
Neoadjuvant chemotherapy todown stage the tumour for
possibility of conservative surgery followed by xrt+/hormonal
Surgery followed by post operative chemo and xrt
Breast Cancer
Role of Radiotherapy
► Conservative therapy:
• In selected cases
• Tumor excision + axillary dissection (or sentinel node)
• Radiotherapy is mandatory
• Results:
• Cosmetic : good to excellent
• Survival rates: equal to those obtained with mastectomy
► Postmastectomy (adjuvant):
• To decrease risk of loco-regional recurrence rates ??
► Preoperative (neoadjuvant):
• To shrink the tumor in locally advanced disease
► Metastatic disease: Palliative (bone, brain metastases)
Breast Cancer
Radiotherapy Techniques-1
► Target Volumes:
• Intact breast and/or chest wall
• ± Regional LN(s): axilla, supraclavicular and internal
mammary
► Methods:
• External Beam:
• Photons: megavoltage, 6 MV
• Electron: boost in conservative therapy, or chest wall
• Brachytherapy: interstitial (boost in conservative therapy)
► Patient positioning & immobilization:
• The arm of involved side: elevated above the head
• The face turned away from the involved side
Simulation & Field Design
•
Supine, ipsilateral arm abducted and externally rotated and head
turned to contralateral side.
•
Medial border at mid-sternum, lateral border placed 2 cm beyond
all palpable breast tissue, inferior border is 2 cm from
inframammary fold and superior border is at head of clavicle or 2nd
intercostal space.
Breast Cancer
Radiotherapy Techniques-2
► Fields arrangement:
• The breast and chest wall: two opposed tangential fields
• The supraclavicular and axillary nodes: anterior field
• The internal mammary nodes: either included within
medial tangential field or in an anterior field
► Dose /Time / Fractionation:
• 50 Gy in 25 fractions over 5 weeks: for microscopic
subclinical disease
• + 15 -20 Gy (boost) : tumor bed (conservative therapy)
► Beam Modifications:
• Wedges within the tangential fields
o
• Angulations of anterior supraclavicular field 15 ?
• Problem of Matching Fields ?
Tangential fields
Anterior Field
(supraclavicular & axillary nodes)
Simulation of tangential fields
Medial tangential field & skin reaction
Chest wall treated with anterior electron beam
Radiotherapy techniques
Tangential fields
Breast irradiation two tangential oppose fields
Skin marks of the treatment fields, left breast
Different Radiotherapy Techniques
• 3 D Conformal
radiotherapy
• IMRT
• Multicatheter
Interstitial
implant
technique
Cont. Different Radiotherapy Techniques
• Mammosite
• Intraoperative
Accelerated Partial
Breast Irradiation
Radiation Techniques
• Dose prescription
• Dose prescribed 45-50 Gy at 1.8-2 Gy/fr
to whole breast with tangential fields and
to supraclavicular fossa ( when included ).
• Boost irradiation with electrons to bring
total tumor bed dose to 60-66 Gy in all pts
underwent BCT and in post mastectomy
pts with positive or closed margin.
Radiation Techniques
• Dose prescription
• Each field should be treated on a
daily basis over the week day.
• Bolus is used in locally advanced
breast cancer
• RT can usually begin within 2-4
weeks of surgery and 3-4 weeks
after last cycle of chemotherapy.
Complication
• Cosmetic
• Arm Edema
• Pneumonitis
• Brachial Plexus Damage
• 2nd Malignancy
Complication
Skin reactions: 4 grades •
Erythema •
Darkdiscolouration •
Dry desquamation •
Wet desquamation •
Follow up
• Every 3 to 6 months for 3 years, then
every 6 to 12 months for 3 years then
every year
• Good history taking with physical
examination , with mammography every
year
• Not routinely recommended for
asymptomatic patients: CXR, Abd . ultra,
bone scan & tumor markers