Download Triple-Negative Breast Cancer

Triple-Negative Breast Cancer
And its Clinical Implication
Background
Definitions and Molecular Features
• Invasive breast cancer
was previously identified
as a homogeneous group
of disease
Definitions and Molecular Features
• Different subgroups exist
 Patient demographics
 Clinical behavior
 Prognosis
Breast Cancer
Basal-like
Subtypes
Luminal
Subtypes
Definitions and Molecular Features
• Molecular genetics
Definitions and Molecular Features
• Triple-negative breast
cancers
Definitions and Molecular Features
• Triple-negative breast
cancers
• Lack the clinical
manifestations of ER,
PR, Her-2 receptors
• Occupy 10-17% of
the breast cancer
population
Immunostaining for ER
Definitions and Molecular Features
• Immunostaining
• Molecular genentics and
cDNA assay
Definitions and Molecular Features
• Basal-like breast cancers
Basal-like breast cancer cells
demonstrating EGFR
immunostaining
Definitions and Molecular Features
• Resemble
myoepithelial cells in
basal layer of ductal
system
Definitions and Molecular Features
• Possess cytokeratins
 CK5
 CK14
 EGFR
• More “progenitor” like
in germline
Definitions and Molecular Features
Overlap
Neg for ER, PR, HER2
Possess cytokeratins e.g.
EGFR, CK15, CK40
Triple-Negative
Breast Cancers
Basal-like Breast
Cancers
BRCA1 mutation
Definitions and Molecular Features
• Triple-negative
breast cancers
Clinical
Negativity for ER,
PR, HER2
• Basal-like breast
cancers
Based on cDNA
assays for
identification of
cytokeratins
CK5, CK14, CK17,
epidermal growth
factor receptors, etc
Definitions and Molecular Features
• The 2 entities are almost
used anonymously in
clinical settings
Patient Demographics
Patient Demographics
• Patient demographics
– Younger age of onset
( <50 years old )
Patient Demographics
• Patient demographics
– Larger mean tumour
size
– Higher rate of node
positivity
1. Abd El-Rehim DM, Pinder SE, Paish CE et al.
Expression of luminal and basal cytokeratins in
human breast carcinoma.
J. Pathol. 2004; 203; 661–671.
2. Fan C, Oh DS, Wessels L et al. Concordance
among geneexpressionbased predictors for breast cancer. N. Engl. J.
Med.
2006; 355; 560–569.
Patient Demographics
• Patient demographics
– Higher histological
grade
1. Fulford LG, Easton DF, Reis-Filho JS et al. Specific morphological features predictive for the basal
phenotype in grade 3 invasive ductal carcinoma of breast. Histopathology 2006; 49;
22–34.
2. Lakhani SR, Reis-Filho JS, Fulford L et al. Prediction of BRCA1 status in patients with breast cancer
using estrogen receptor and basal phenotype. Clin. Cancer Res. 2005; 11; 5175–5180.
3. Livasy CA, Karaca G, Nanda R et al. Phenotypic evaluation of the basal-like subtype of invasive
breast carcinoma. Mod. Pathol. 2006; 19; 264–271.
4. Tsuda H, Takarabe T, Hasegawa F, Fukutomi T, Hirohashi S. Large, central acellular zones indicating
myoepithelial tumor differentiation in high-grade invasive ductal carcinomas as markers of predisposition
to lung and brain metastases. Am. J. Surg. Pathol. 2000; 24; 197–202.
5. Tsuda H, Takarabe T, Hasegawa T, Murata T, Hirohashi S. Myoepithelial differentiation in high-grade
invasive ductal carcinomas with large central acellular zones. Hum. Pathol. 1999; 30; 1134–1139
Patient Demographics
• Patient demographics
– More aggressive
clinical behavior
1. Nielsen TO, Hsu FD, Jensen K et al.
Immunohistochemical and clinical
characterization of the basal-like subtype of
invasive breast carcinoma. Clin. Cancer Res.
2004; 10; 5367–5374
2. Abd El-Rehim DM, Pinder SE, Paish CE et al.
Expression of luminal and basal cytokeratins in
human breast carcinoma. J. Pathol. 2004; 203;
661–671.
3. Fan C, Oh DS, Wessels L et al. Concordance
among geneexpression-based predictors for
breast cancer. N. Engl. J. Med. 2006; 355; 560–
569.
Clinical Implication
• Reason for isolating a
subgroup of breast
cancer ?
Clinical Implication
• Clinical implications ?
Clinical Implication
• Does it affect our way of
treating our patients ?
Clinical Implication
• Let’s utilize a clinical
scenario for illustration
Clinical Implication
Clinical Implication
• Treatment options
Surgery
• BCT vs Total
mastectomy ?
Surgery
• More aggressive
clinical behaviour
• Larger tumour size
• Higher rate of axillary
LN positivity
• Higher histological
grade
Clinical Implication
• No difference in
locoregional
recurrence between
mastectomy group
and BCT with
radiation group when
multivariate
regression was
applied
1. Bruce G. Haffty, Qifeng Yang, Michael Reiss,
et al. Locoregional Relapse and Distant
Metastasis in Conservatively Managed Triple
Negative Early-Stage Breast Cancer. J Clin Onc,
2006. 24; 36; 5652-5657
2. Gary M. Freeman, Penny R. Anderson, Tianyu
Li, Nicos Nicolaou. Local-Regional Recurrence of
Triple Negative Breast Cancer after BreastConserving Surgery and Radiation. Cancer. 2009.
115(5): 946-951
3. Parker C.C., Smith M.H., Henderson B.D. Li,
Ampil F., Chu Q.D. Breast Conservation Therapy
Is a Viable Option for Patients with TripleReceptor Negative Breast Cancer.
Clinical Implication
• TNBC is not a sole
indicator for / against
mastectomy
• Factors which
determine BCT /
mastectomy :
– E.g. multicentricity,
tumour size
Chemotherapy
• Neo-adjuvant
Therapy ?
• Adjuvant Therapy ?
Clinical Implication
• Lack of ER, PR
• No role of hormonal
therapy
• Lack Her-2 receptor
• No role for current
targeted therapy
towards Her-2
receptor
Clinical Implication
• High chemosensitivity
• Higher rate of
achieving complete
pathological
remission CR ( 36% )
1. Carey LA, Dees EC, Sawyer L, et al. The triple
negative paradox: primary tumour
chemosensitivity of breast cancer subtypes. Clin
Cancer Res. 2007;13(8):2329-2334
Clinical Implication
• In patients achieving
CR, survival similar to
patients in non-TNBC
group
• Residual disease
1. Carey LA, Dees EC, Sawyer L, et al. The triple
negative paradox: primary tumour
chemosensitivity of breast cancer subtypes. Clin
Cancer Res. 2007;13(8):2329-2334
Clinical Implication
1. Carey LA, Dees EC, Sawyer L, et al. The triple negative paradox: primary tumour chemosensitivity of
breast cancer subtypes. Clin Cancer Res. 2007;13(8):2329-2334
Chemotherapy
• Are we giving neo-adjuvant Therapy ?
Clinical Implication
• Aim
– Downstage
– Downsize
• To achieve
resectability of the
tumour
Chemotherapy
• How about adjuvant chemotherapy ?
Clinical Implication
• St. Gallen consensus
recommendations
– Tumor size >2 cm
– ER and PR negativity
– Tumor histologic grade
2 or 3
– Age <35 years
– Nodal involvement
Clinical Implication
• Prognosis
• Long-term
surveillance
Clinical Implication
• Poorer prognosis
• Higher mortality
• Reduced overall
survival and diseasefree survival
1. Carey LA, Dees EC, Sawyer L, et al. The triple
negative paradox: primary tumour
chemosensitivity of breast cancer subtypes. Clin
Cancer Res. 2007;13(8):2329-2334
Clinical Implication
• Patient demographics
– More frequent
haemaogeneous
spread
• Lungs
• Brain
– Much less spread to
lymphatics and bones
1. Fulford LG, Reis-Filho JS, Ryder K et al. Basallike grade III invasive ductal carcinoma of the
breast: patterns of metastasis and long-term
survival. Breast Cancer Res. 2007; 9; R4.
2. Hicks DG, Short SM, Prescott NL et al. Breast
cancers with brain metastases are more likely to
be estrogen receptor negative, express the basal
cytokeratin CK5 ⁄ 6, and overexpress HER2 or
EGFR. Am. J. Surg. Pathol. 2006; 30; 1097–1104.
3. Rodriguez-Pinilla SM, Sarrio D, Honrado E et
al. Prognostic significance of basal-like
phenotype and fascin expression in nodenegative invasive breast carcinomas. Clin.
Cancer Res. 2006; 12; 1533–1539.
4. Tsuda H, Takarabe T, Hasegawa F et al. Large,
central acellular zones indicating myoepithelial
tumor differentiation in high-grade invasive ductal
carcinomas as markers of predisposition to lung
and brain metastases. Am. J. Surg. Pathol. 2000;
24; 197–202
Clinical Implication
• Increased rate of
loco-regional
recurrence
• Earlier relapse
• Shorter postrecurrence survival
1. Liedte C, Mazouni C, Hess KR, et al.
Response to neoadjuvant therapy and long-term
survival in patients with triple-negative breast
cancer. J Clin Oncol. 2008;26(8);1275-1281
Figures in NTWC
• During the period from 1 Jan 2010 to 31 Dec
2010
• Total no. of 176 breast cancers
• 12 cases of triple negative breast cancers
( 6.9% )
Summary
• Triple negative breast cancer
• Special breast cancer subgroup
• Different patient demographics and different
clinical behaviour
• Treatment options
• Subgroups of TNBC ?
• New therapeutic agents targeted at the surface
molecular markers under development
• Direction for the future development of modern
medicine in breast cancer