Recent advances in carcinoma breast

1. Dr kundan
Junior Resident , Department of surgery
Patna medical college & Hospital

2.  Risk assessment tools
 Imagings
 Non Palpable Lesions and Localization
Techniques
 Biomarkes
 Genomic analysis
 Surgery
 Chemoprevention
 Chemotherapy

3.  Gail model-focuses primarily on nongenetic risk factors, with limited
information on family history
 Claus model- based on empiric data from the Cancer and Steroid
Hormone Study
Estimates a woman’s risk of breast cancer based on her age, the
number of first- and second-degree relatives with breast cancer (up to two);
and their age at onset.
 BRCAPRO
incorporates BRCA1 and BRCA2 mutation frequencies,
cancer penetrance in mutation carriers, cancer status (affected,
unaffected, or unknown), and age of the patient's first-degree and
second-degree relatives.
 The Breast Cancer Risk Assessment Tool
 Cuzick–Tyrer model
- includes history of benign breast disease
estrogen exposure

4.  Does the woman have a medical history of any breast cancer or of
ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) or has she
received previous radiation therapy to the chest for treatment of Hodgkin
lymphoma?
 2. Does the woman have a mutation in either the BRCA1 or BRCA2 gene, or a
diagnosis of a genetic syndrome that may be associated with elevated risk of breast
cancer?
 3. What is the woman's age?
This tool only calculates risk for women 35 years of age or older.
 4. What was the woman's age at the time of her first menstrual period?
 5. What was the woman's age at the time of her first live birth of a child?
 6. How many of the woman's first-degree relatives - mother, sisters, daughters -
have had breast cancer?
 7. Has the woman ever had a breast biopsy?
 7a. How many breast biopsies (positive or negative) has the woman had?
 7b. Has the woman had at least one breast biopsy with atypical hyperplasia?
 8. What is the woman's race/ethnicity?
 8a. What is the sub race/ethnicity?

5. luminal B ER/PR + Her-2/neu +
Basal-like ER/PR - Her-2/neu -
luminal A ER/PR + Her-2/neu -
Her-2
overexpressing
ER/PR - Her-2/neu +
HER-2 positive and triple negative
subtypes have been shown to
preferentially metastasize to the brain
over the other subtypes

6.  Full-field digital mammography -superior to standard mammography in
women under 50 years of age and in those with dense breasts.
 Computer-Aided Detection
CAD programs are commercially available systems that use computer
software to assist the mammographer in detecting or identifying potentially
suspicious abnormalities on a mammogram. The CAD program identifies potential
abnormalities on the images and marks areas on the study that the computer
considers to be suspicious.
 DYNAMIC MRI –
Contrast enhancement with Gd-DTPA
The cancers are found to have rapid wash-in of contrast and either a
rapid wash-out of contrast or a leveling off of contrast.
These two patterns of dynamic contrast enhancement yields
91% sensitivity and 83% specificity for malignancy detection.

7.  Positron-Emission Mammography-
Most breast malignancies have greater metabolism than normal tissues
and concentrate 18F- fluorodeoxyglucose(FDG)
 Molecular breast imaging

8.  utilizes small semiconductor-based γ-cameras in a mammographic
configuration to provide high-resolution functional images of the breast.
 have used Tc-99m sestamibi,
 Imaging can be performed within 5 min postinjection, with the breast
lightly compressed between the two detectors. Images of each breast are
acquired in the craniocaudal and mediolateral oblique projections
facilitating comparison with mammography.
 overall sensitivity of 90%, with a sensitivity of 82% for lesions less than 10
mm in size

9.  Digital Infrared Imaging
 based on the principle that metabolic activity and vascular circulation in
both pre-cancerous tissue and the area surrounding a developing breast
cancer is almost always higher than in normal breast tissue

10.  3-dimensional (3-D) imaging technology
 reduces or eliminates the tissue overlap
effect

11.  non-palpable lesions are associated with
both a lower stage of disease and a
substantially decreased incidence of lymph
node involvement
 Wire localization (WL)-
pain and discomfort
dislodgement of the wire,
intraoperative wire transection,
retention of wire fragments,
thermal injury with the use of cautery,
hematoma
syncope

12.  Radioguided occult lesion localization (ROLL)
injection of a nuclear tracer (99 m TC-labelled
colloidal albumin) directly around the tumor under ultrasound or
stereotaxic guidance
the excision of the primary tumor is guided by a gamma
probe, and a sentinel node biopsy can be performed at the same time if
needed
 intraoperative ultrasound (IOUS).

13.  used to collect cellular material for cytomorphology and
biomarker studies
 cellular material is retrieved by inserting a 1.5-cm flexible
microcatheter through through the nipple surface orifices
under local anesthesia and infusing the same with saline
 uses of ductal lavage include
selection of women for risk-reduction therapy,
diagnostic workup of a nipple discharge,
early diagnosis of an occult cancer
monitoring response,
study genetic alterations
In conjunction with the newly identified genetic markers, ductal lavage has the
potential to identify early breast cancers before any mammography changes occur.
It can be used to study breast epithelial cells at the molecular level.
Limitations of ductal lavage are its time-consuming nature, inability to detect extra-
ductal carcinoma, and uncertainty about its sensitivity and specificity.

14.  Indices of proliferation : PCNA , Ki67
 Indices of apoptosis : bcl2 , bcl2/bax ratio
 Indices of Angiogenesis :VEGF ,
ANGIOGENESIS INDEX
 Growth factor receptors : EGFR , Her2/neu

15.  The 21-Gene Recurrence Score (RS)
(Oncotype DX) is an RT-PCR based gene
expression profiling assay that includes 16
cancer genes and 5 reference genes
 Mama print – another assay based on 70
genes

16. PROLIFERATION
Ki-67
STK15
Survivin
Cyclin B1
MYBL2
ESTROGEN
ER
PR
Bcl2
SCUBE2
INVASION
Stromelysin 3
Cathepsin L2
HER2
GRB7
HER2
BAG1GSTM1
REFERENCE
Beta-actin
GAPDH
RPLPO
GUS
TFRC
CD68
Category RS (0 – 100)
Low risk RS < 18
Int risk RS ≥ 18 and <
31
High risk RS ≥ 31

17.  Surgical management of breast cancer has
shifted from extensive and highly morbid
procedures, to the modern concept obtaining
the best possible cosmetic result in tandem
with the appropriate oncological resection.

18.  William Halsted popularized radical mastectomy in 1894.Radical
mastectomy (RM) resulted in a significant drop in the local recurrence
rate, but the curative potential remained limited.
 MRM is a less morbid procedure compared to RM, the patient will still
require a loss of the breast. The attempt to preserve the breast without
compromising survival brought up the use of Breast Conserving Therapy
(BCT)
 This includes breast conserving surgery and breast radiotherapy.
 BCS is an important part of the breast-conserving therapy, which may be
defined as a combination of conservative surgery for resection of the
primary tumor with or without surgical staging of the axilla, followed by
radiotherapy for the eradication of the residual microscopic disease of
the breast, with or without adjuvant systemic therapy.

19.  ELIGIBLITY CRIETERIA
– Ability to obtain a margin negative lumpectomy
- capability to deliver breast irradiation
- likely hood of achieving a cosmetically acceptable result
 EXCLUSION CRIETERIA
- multicentric disease
- diffuse malignant appearing microcalcificaton
- prior therapeutic chest irradiation
- associated contraindication to radiation
- positive margin on lumpectomy/reexcision specimen
- history of collagen vascular disease
- tumor size > 5 cm

20.  The incision should be sited in such a way that if mastectomy is
eventually required, it can be included in the mastectomy
specimen. In the upper part of the breast, incisions should be
curvilinear or transverse, while in the lower part, they should be
either curvilinear or radial.
 Resection of 0.5 to 1.0 cm of grossly normal tissue resulted in a
histologically negative margin in 95% of patients.
 In order to ascertain a negative margin, intraoperative margin
assessment (IOMA) has been found to be useful. These include:
gross inspection in the operating room, with or without frozen section analysis,
cytologic touch prep (CTP) analysis,
shaved margin (SM),
intraoperative ultrasound (IOUS).
 Drainage of the lumpectomy cavity should be avoided and it
should be allowed to fill with serum and fibrin. This will give the
best cosmetic result.

21.  COMPLICATIONS :
Seroma formation,
arm morbidity (arm swelling, arm pain, arm numbness, arm
stiffness, shoulder stiffness, shoulder pain, and nerve injury),
phantom breast syndrome,
delayed cellulitis
pain syndromes of the chest wall, axilla, and upper
extremity

22.  skin sparing mastectomy (SSM) was first used
by Toth and Lappert in 1991
 removes the breast, nipple-areola complex,
previous biopsy incisions, and skin overlying
superficial tumors
 Preservation of the inframammary fold (IMF)
and native skin greatly enhances the
aesthetic result of breast reconstruction.
 The thickness of the mastectomy flaps should
be the same as in a conventional
mastectomy.

25.  In radiofrequency ablation, high-frequency
alternating current is delivered via an electrode
inserted into the tumor under ultrasound
guidance. Pilot studies have shown that this
technique have confirmed its efficacy to kill
tumor cells. Similarly cryosurgery and focused
ultrasound are currently under investigation in
breast cancer. Percutaneous tumor excision is
another novel technique in which small breast
tumors are extracted via plastic cannulas
attached to a circular blade. The lesion in
question is targeted and retrieved with the
assistance of mammographic stereotactic
localization.

26.  MammoSite involve a reasonably user-friendly inflatable balloon that is
inserted into the lumpectomy cavity either in the operating room or
postoperatively, under ultrasound guidance.
 Radioactive sources in form of interstitial catheters are placed in the
tumor bed intra-or post-operatively offers several advantages over
traditional external beam radiation.
 It reduces the treatment time from 5 to 7 weeks to 4 to 5 days.
 It allows restriction of the radiation dose to the tumor bed compared
with conventional radiation therapy
 Older brachytherapy catheters were bulky and cumbersome. Newer
devices, such

27.  There are two required components for BCT. First, tumors must
be resectable with a pathologically clear margin, that is, a
surrounding margin of breast parenchyma without disease.
Secondly, patients undergoing partial mastectomy typically
receive whole breast irradiation to achieve local control in the
breast.
 Tumor size must be sufficiently small relative to the entire
breast, such that the appearance of the breast is cosmetically
acceptable following partial mastectomy. Additionally, all
suspicious findings on imaging must be resectable with the partial
mastectomy. The presence of diffuse highly concerning
microcalcifications on mammography is a contraindication to
BCT. Pregnancy and a history of previous chest irradiation do not
allow BCT, as they are contraindications to the requisite
postoperative radiotherapy. Positive margins after BCT require a
repeat attempt at excision or completion mastectomy to achieve
clear margins. Findings of involved margins with partial
mastectomy significantly increase the chance of disease
recurrence

28.  A recent trend including surgery as cancer
prevention has gained wide acceptance.
Contralateral prophylactic mastectomy (CPM)
has been found to decrease the risk of
development of a cancer in the disease-free
breast in women at high risk.
 BRCA mutation or a strong family history of
breast cancer
 LCIS,

29.  Bilateral prophylactic salpingo-oophorectomy
is widely used for cancer risk reduction in
premenopausal women with BRCA1/2
mutations.[47-49]
Bilateral prophylactic salpingo-
oophorectomy significantly reduces breast
cancer risk by approximately 50% and ovarian
cancer risk by 80% to 95% but may be
accompanied by menopausal symptoms,
increased cardiovascular risk, impaired
quality of life, and accelerated bone loss

30.  circulating tumor cells (CTCs)
 enrichment of CTCs by antibody-mediated
targeting of the epithelial cell adhesion
marker (EpCAM)
 greater than five CTCs is the breaking point
for a poor prognosis in breast cancer

31. Breast Cancer Subtypes Have
Distinct Treatment Options
Endocrine
Therapy
Trastuzumab Chemo
Luminal A Yes No Yes
Luminal B Yes Y/N Yes
HER2 No Yes Yes
Basal-like No No Yes

36.  Advances in Her-2/neu overexpressed breast
cancer
 •Trastuzumab in adjuvant, neoadjuvant, and
metastatic setting
 •Lapatinib in neoadjuvant and metastatic
settings
 •Pertuzumab, TDM-1 (Katherine trial) in
neoadjuvant, adjuvant and metastatic settings
 • Combinations of Her-2/neu inhibitors

37.  Neoadjuvant Chemotherapy (NACT)
 •Goal is to optimize surgical outcomes
 •Standard for larger, Stage 3 tumors
 • Marginally resectable tumor
 • Inflammatory breast cancer
 • Best outcome is pathologic complete response path CR
 • Surgery is ALWAYS perfomed, regardless of outcome of chemotherapy

38.  SERM – tamoxifen , raloxifen
 AROMATASE INHIBITOR – Exemestane
Anastrazole
Leterazole

39.  HER2/NEU – trastuzumab,
ado-trastuzumab emtansin
pertuzumab
laptanib
 mToR inhibitor – everolimus
 PARP (poly ADP ribose polymerase) inhibitor -Iniparib
BRCA MUTATION INHIBITORS Olaparib
veliparib

40. Lapatinib
• Binds to intracellular ATP binding
site of EGFR (ErbB-1) and HER2
(ErbB-2) preventing
phosphorylation and activation
• Blocks downstream signaling
through homodimers and
heterodimers of EGFR (ErbB-1) and
HER2 (ErbB-2)
• Dual blockade of signaling may be
more effective than the single-
target inhibition provided by
agents such as trastuzumab
1+1 2+2 1+2
Lapatinib
Downstream signaling
cascade
Rusnak et al. Mol Cancer Ther 2001;1:85-94; Xia et al. Oncogene 2002;21:6255-6263;
Konecny et al. Cancer Res. 2006;66:1630-1639

41. Oncotype Dx: Genomic Stratification of
Luminal Breast Cancers for Therapeutic
Benefit
The 21-Gene
Recurrence Score
(RS) (Oncotype DX) is
an RT-PCR based
gene expression
profiling assay that
includes 16 cancer
genes and 5
reference genes.
PROLIFERATIONPROLIFERATION
Ki-67Ki-67
STK15STK15
SurvivinSurvivin
Cyclin B1Cyclin B1
MYBL2MYBL2
ESTROGENESTROGEN
ERER
PRPR
Bcl2Bcl2
SCUBE2SCUBE2
INVASIONINVASION
Stromelysin 3Stromelysin 3
Cathepsin L2Cathepsin L2
HER2HER2
GRB7GRB7
HER2HER2
BAG1BAG1GSTM1GSTM1
REFERENCE GENESREFERENCE GENES
Beta-actin, GAPDH, RPLPOBeta-actin, GAPDH, RPLPO
GUS, TFRCGUS, TFRC
CD68CD68

42. PROLIFERATION
Ki-67
STK15
Survivin
Cyclin B1
MYBL2
ESTROGEN
ER
PGR
Bcl2
SCUBE2
INVASION
Stromolysin 3
Cathepsin L2
HER2
GRB7
HER2
GSTM1
REFERENCE
Beta-actin
GAPDH
RPLPO
GUS
TFRC
CD68
BAG1