ROLE OF MOLECULAR PATHOLOGY

IN ASSISTING DIAGNOSIS OF
BREAST CANCER
C O U R S E : PAT H 6 2 0 0 – T E C H N I Q U E S A N D A P P L I C AT I O N S O F M O L E C U L A R PAT H O L O G Y
N A M E : L E E K A WA I J E N N Y
S T U D E N T N U M B E R : 2 0 0 7 9 4 4 3 2 2
 USING MOLECULAR TESTING TO
UNDERSTAND BREAST CANCER
• Categorize breast cancer in different molecular
subtypes
• Investigate etiology of breast cancer
• Assist treatment decisions
 CATEGORIZE BREAST CANCER IN
DIFFERENT MOLECULAR SUBTYPES

• Molecular Subtypes:
1. Hormone receptor (Luminal A & B)
2. HER2 related
3. Basal-like

- Using genomic DNA, DNA methylation, exome sequencing,

microRNA sequencing and reverse-phase protein assays.
HORMONE RECEPTOR (LUMINAL A & B)

• Luminal cancers express hormone receptors and are lower

grade, in contrast, HER2 subtypes are higher grade.
• Luminal A & B are ER-related genes (ER+, where A>B)
• Luminal A is a lower grade than Luminal B in histologic
correlation.
• Luminal B cancers have a worse prognosis than luminal A and
associated with BRCA2 tumors.
• Hormone responsive
• Treatment: Hormone therapies
 HER2-RELATED

• HER2 gene also known as the human epidermal growth factor

receptor-2
• Located at 17q12-21.32
• More aggressive than other types of breast cancer
• Less responsive to hormone treatment
• FISH is the gold-standard
• Treatment: HER2-targeted therapies
 BASAL-LIKE

• Overlap substantially with the population of breast cancers of

“triple negative”
• Triple negative – ER-, PR- & HER2-
• But cytokeratin (CK) 5/6 or epidermal growth actor receptor
(EGFR)+
• BRCA1-associated breast cancer in majority
• Higher response to chemotherapy
ASSOCIATION BETWEEN HEREDITARY BREAST
CANCERS AND MOLECULAR SUBTYPES
INVESTIGATE ETIOLOGY OF BREAST CANCER

• Basically, divided into two categories: ER+ and ER-

• ER+: deletions of 16q and gains of 1q
• ER-: p53 mutations, HER2 amplifications, BRCA1
dysfunction.
 A MODEL OF THE MOLECULAR
PATHOGENESIS OF BREAST CANCERS
 MOLECULAR TESTING ASSISTS
TREATMENT DECISION MAKING
• Methods:
- ER & PR: Immunohistorchemistry (IHC)
- HER2: IHC or FISH
- BRCA1 & 2: PCR

• Panel-based molecular testing can help to predict both

prognosis and response to therapy
- Predict need/response to hormones and HER2-targeted
therapies, and also for chemotherapy
 ADVANTAGES, PROBLEMS,
LIMITATIONS AND RESEARCH GAPS
• Assisting on therapeutic decision making
• Advantages, problems and limitions on genetic testing and
molecular pathological testing.
• Future goal
 REFERENCE
1. http://www3.ha.org.hk/cancereg/statistics.html Hong Kong Cancer Registry.
2. Kimberly H. Allison, MD. (2012) Molecular Pathology of Breast Cancer. American Journals Clinical Pathology
2012;138:770-780
3. Ana B. Espinosa, PhD, Maria D. Tabernero, MD, PhD, et al. (2003) Her-2/neu Gene Amplification in Familial vs
Sporadic Breast Cancer American Journals Clinical Pathology; 2003; 120:917-927
4. http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA National Cancer Institute.
5. Allen M Gown (2008) Current issues in ER and HER2 testing by IHC in breast cancer Modern Pathology (2008)
21, S8–S15
6. Sunil R. Lakhani, Marc J. van de Vijver, et al. (2002) The Pathology of Familial Breast Cancer: Predictive Value
of Immunohistochemical Markers Estrogen Receptor, Progesterone Receptor, HER-2, and p53 in Patients With
Mutations in BRCA1 and BRCA2. American Society of Clinical Oncology 2002: 2310-2317
7. A.M. Martin, M.A. Blackwood, et al. (2001) Germline Mutations in BRCA1 and BRCA2 in Breast-Ovarian
Families From a Breast Cancer Risk Evaluation Clinic. American Society of Clinical Oncology. 2001: 2247-
2253
8. Paraskevi Apostolou and Florentia Fostira (2013) Hereditary Breast Cancer: The Era of New Susceptibility
Genes. BioMed Research International 2013; 2013: 747318.
9. Alastair Thompson, Keith Brennan, et al. (2008) Evaluation of the current knowledge limitations in breast cancer
research: a gap analysis. Breast Cancer Res. 2008; 10(2): R26.
10. Martin J. Larsen, Troben A Kruse, et al. (2013) Classifications within Molecular Subtypes Enbles Identification
of BRCA1/2 Mutation Carries by RNA Tumor Profiling PloS One. 2013: 8(5): e64268