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BREAST CANCER (Pathology (Non-invasive carcinoma (in situ) (Ductal…
BREAST CANCER
Pathology
Non-invasive carcinoma (in situ)
Ductal
carcinoma in situ (DCIS):
Visible on mammography
(
microcalcifications
or
non-palpable
tumor)
high risk of progression
Progression at the site of in situ disease
Progression to ductal carcinoma
Lobular
carcinoma in situ (LCIS):
Asymptomatic
(
found on biopsy only
)
low risk of progression
Risk of progression
identical in both breasts
Risk of progression
identical for ductal and lobular carcinoma
Invasive
carcinoma:
Infiltrating
carcinoma, no special type (
ductal
)
Infiltrating
lobular
carcinoma
Medullary
,
mucinous
, and
tubular
carcinomas
Specific clinico-pathological entities:
Inflammatory
carcinoma
Paget’s
disease
non-epithelial tumors: sarcomas, lymphomas
required additional information
grade
(eg.
Bloom-Richardson
: atypia, mitoses, tubular
structure formation),
steroid receptors
(ER, PgR),
HER2
,
Ki67
,
location
and
number of involved nodes
, extracapsular invasion
Incidence
of major histologic types
Ductal: 80
%,
lobular 10
,
medullary 5
treatment
Systemic
chemotherapy
alkylating
agents:
cyclophosphamide
antimetabolites
:
methotreksate
, 5-
fluorouracil
, gem
citabine
,
capecitabine
antracycline
: doxo
rubicin
, epirubicin
vinca
alkaloids: vinorelbine
taxanes
: docetaxel, paclitaxel
multidrug regimens
FAC/FEC, AC/EC
AT, TAC
vinorelbine + doxorubicin, 5-fluorouracil lub mitoxantron
docetaxel + capecitabine
hormonotherapy = estrogen depletion
estrogen source ablation: castration (surgery or RT), adrenalectomy
removal or inhibition of gonadotropin action: hypophysectomy, LHRH agonists, progestins, danazol
estrogen receptor blocking: tamoxifen and other SERM, fulvestrant
inhibition of peripheral estrogen synthesis: aromatase inhibitors
ablative methods
castration
surgical - laparoscopy, radiological - slower effect, well tolerated
adrenalectomy, hypophysectomy (historical)
tamoxifen
estrogen receptor antagonist
partial agonistic effect: endometrium, bone mineral density, lipid metabolism
biological (targeted) therapy
HER-2 (Human Epidermal growth factor Receptor-2)
gene amplification and/or receptor overexpression – 20% tumors
Her-2 (+) – worse prognosis, decrease DFS and OS
anti-HER2 therapies
patient selection:
IHC:
0, 1+ - no indication
2+ - questionable indication (to be verified by FISH)
3+ - undoubtful indication
FISH:
no amplification - no indication
amplification present– undoubtful indication
local therapy
Early BC
mastectomy (+/- postoperative RT)
removal of breast (without pectoralis major muscle)
removal of axillary lymph nodes:
-Sentinel node biopsy
-Breast Conserving Therapy: removal of tumor with a margin
of heathy tissue (quadrantectomy, segmentectomy, wide local excision), breast radiotherapy
Breast Conserving Therapy
Patient selection: tumor < 2-3 cm, unifocal lesion, no contraindications for RT, availability of good cosmesis, patient’s will
brachytherapy
Outcome
local recurrence: 0,5-1%/year
survival – equivalent to post-mastectomy
cosmesis depends on: type of surgery, RT dose, boost technique, breast size
Post-mastectomy RT
Indications
positive surgical margin
tumor
> 5 cm
involvement of
> 3 axillary nodes
extracapsular
invasion
systemic therapy
Early BC
Adjuvant systemic therapy
Methods:
chemotherapy (CMF, FAC/FEC, AC/EC, taxanes)
hormonotherapy:
premenopausal (tamoxifen, castration)
postmenopausal (tamoxifen,IA)
targeted therapy
Locally Advanced BC
T3-4 and/or N2-3, M0
usually starts with systemic therapy (anthracycline/taxane based ChT)
local treatment:
•radiotherapy (techniques: like early BC, higher doses: up to > 70 Gy to breast)
•surgery in selected cases (value non-confirmed)
Hormonotherapy, anti-HER2 therapy following ChT
elderly patients – hormonotherapy only (in selected cases)
Locoregional recurrence
Within breast after Breast Conserving Therapy:
best prognosis, treatment: mastectomy
Within chest wall after mastectomy
surgery – if possible, RT in non-irradiated patients, re-irradiation in selected patients (limited area)
In regional lymph nodes:
surgery – if possible, RT in non-irradiated patients
Metastatic BC
Differential diagnosis
lung
: lung cancer, carcinoid, TBC
CNS
: meningioma
liver
: hemangioma, cyst, teratoma
bones
: trauma,
Treatment aims
improvement of
QoL
,
prolongation of survival
prognostic factors
intrincis
phenotype
site of metastatic
involvement
number of metastases
disease
free interval
Good prognosis
skin, soft tissue, bone, single lung lesions
Poor prognosis
liver, brain, spinal cord, bone marrow, lung- lymphangitis, peritoneum
treatment
local treatment
surgery
pathological fractures
single brain metastases (rarely)
spinal cord compression (especially in case of pathological fractures)
radiotherapy
bone, brain metastases
spinal cord compression
soft tissue lesions
supportive treatment
Bisphosphonates
/
denosumab
( bone metastases, hiperkalcemia)
steroids
(brain metastases, spinal cord compression, visceral metastases)
analgesics
psycho-oncology
(pharmacotherapy, psychotherapy)
systemic
hormonotherapy, chemotherapy, targeted therapy
choice of systemic therapy*
targeted therapy
trastuzumab (Herceptin)
humanized monoclonal antibody against HER-2 combined with ChT or HT – improves efficacy
lapatinib
small molcules - inhibitor of tyrosine kinase of HER2 and EGFR
conclusions
HTH is a treatment of choice for most patients
In case of response to 1st line HTH, treatment should proceed with 2nd line HTH
ChT is indicated in case of ER/PgR (-), rapid progression and lack of response to earlier HTH
In tumors overexpressing HER2 ChT/HT should be combined with anti-HER2 therapy
DIAGNOSIS
obligatory
:
history + clinical
examination,
mammography, biopsy, chest X-ray
.
Depending on stage
and clinical situation:
galactography
, breast
ultrasound
, breast
MRI
, chest
CT
,
abdominal CT or ultrasound
,
brain CT or MRI
,
bone X-ray or scan
,
FNAB of suspicious lesions
distant
metastases
Chest
: X-ray/CT,
Abdomen
: US/CT/MRI,
Brain
: CT/MRI,
Bone
: X-ray/bone scan/CT/MRI,
biopsy of suspicious lesions, bone marrow biopsy, cytology of effusions
Biopsy of breast
lesions
Excision biopsy
( tumor size + histopatology)
Thru-cut biopsy
,
incision biopsy
(histopatology)
FNB
(cytology)
Full thickness skin biopsy
Diagnostic algorithm*
risk factors
age (80% after 50)
,
estrogens
(early menarche, late menopause, hormone replacement therapy, oral contraception, abortions)
breast feeding (protective)
pregnancy - temporary increase of risk (during pregnancy), afterwards decrease the risk
nulliparity, 1st pregnancy after 30
.
diet and
lifestyle
ionizing
radiation
benign breast diseases and precancerous lesions
(carcinoma in situ, atypical hyperplasia)
hereditary and
genetic
predisposition (25% cases):
-
Ca in mother and sister
: 14x increase risk
-
syndromes
:
BRCA1
(+ ovarian cancer),
BRCA2
(
male breast cancer
),
Li-Fraumeni
syndrome (+ leukemias, soft tissue sarcomas, brain tumors, adrenal cortex cancers),
Cowden’s
syndrome (+ skin teratomas), AT (heterozygotes ~ 7% of breast cancers),
Lynch II
syndrome,
Peutz-Jaeghers
syndrome,
Klinefelter
syndrome
race
(
Jewish
in Israel : 4x higher risk than non-Jewish)
social
status
history
of breast cancer - (
esp. lobular
) – 5x higher risk than general population
history of
other malignancies
(
ovarian
cancer,
colorectal
cancer,
prostate
cancer (family history))
prophylaxis
primary
:
-
avoiding
risk factors
-
chemoprevention
:
tamoxifen
( decrease incidence, increase thromboembolic complications, increase endometrial hyperplasias/cancer)
raloxifen
(treatment of osteoporosis, decrease incidence, no increase of endometrial cancer)
screening
mammography
decreased mortality
recommended since the age of 50.
Cons:
ionizing radiation exposure, psychological distress, unnecessary biopsies and surgeries, false feeling of security, cost, time
Signs and symptoms
lump
, skin
dimpling
, skin
colour or texture change
, how the nipple looks (
pulling in of the nipple
),
clear or bloody nipple discharge
.
skin
involvement (infiltration or ulceration,
„peau d’orange”
,
satelite
nodules)
arm edema
(massive nodal involvement)
symptoms of distant metastases
Spread to lymph nodes
Mediastinal
,
internal mammary
,
interpectoral
(
Rotter's
), supraclavicular, subclavicular, distal (upper) axillary, central (middle)
axillary
, proximal (lower) axillary
metastases
CNS
,
lymph nodes
,
skin
,
pleura
,
lung
,
liver
,
bones
Prognosis
classical factors
Number of positive axillary nodes
Tumor
size
Lymphatic and vascular invasion
Histologic type, grade
Estrogen/progesterone receptors
HER2/neu overexpression
proliferation (Ki67)