Target therapy for HER2 positive breast Ca

Breast Imaging Reporting And Data System(The American College of Radiology

(ACR)
BI-RADS
assessment
Report(Impression) Risk of Follow-up
Cancer%
categories
0 Inconclusive result 0 Additional imaging investigation &
evaluation require
1 Negative finding 0 Annual screening mammography

2 Benign finding 0 Annual screening mammography

3 Probably benign <2% Receive 6 month follow-up mammogram

finding
4 Suspicious for 3-94% May require biopsy
malignancy
5 Highly suggestive >95% require biopsy
malignancy
6 Known biopsy-proven 100%
malignancy
high levels of Ki-67 indicate faster growth of cancer cells
molecular subtypes based on the genes the cancer cells express, which control how
the cells behave.

• 5 molecular subtypes • Luminal

1. Luminal A -ER positive +/- PR
2. Luminal B HER2 negative positive -75-80% of breast
ca
3. Luminal B HER2 positive
(luminal B-like breast ca) • Non-Luminal
4. Non-Luminal HER2 positive
-ER and PR negative
-20-25% of breast ca
5. Triple negative (TNBC)
(basal-like breast cancer)
-more common in younger woman with
BRCA1 gene mutation
Breast cancer Gene / protein identified:

• BRCA1 (BReast CAncer gene 1) -gene is located at chromosome

17q21
• BRCA2 - gene is located at chromosome 13q12.3
• ER/PR,
• ERBB2/HER-2 (neu oncogene)
• PL3KCA (Phosphatidylinositol 3-kinase)
• PDL1, MSI, TNB, PALB2, PTEN
What are BRCA1 and BRCA2?

• genes that produce proteins that help repair damaged DNA.

• Everyone has two copies of each of these genes, one copy inherited from each
parent.
• called tumor suppressor genes because when they are harmful (or pathogenic)
variants (or mutations), cancer can develop.
• A harmful variant can be inherited from either parent. 50% chance of inheriting
the mutation.
• 55/45-70%women who inherit a harmful BRCA1/BRCA2 variant will develop
breast cancer by 70–80 years of age.
• risk of developing cancer in the (contralateral) breast 30% after 10 years/50%
after 20 years
Her2 signaling pathway in breast cancers.
targeted cancer therapy
How does it work?

• interferes with proteins on cancer cell surface to block it growth

• interferes with signals to make new blood vessels
• Attach and produce the cell-killing substances to targets on cancer cell
surface.
• prevent specific hormones from being taken up by cancer cells.
• 25% of breast cancers, a gene human epidermal growth receptor 2 (or HER2/neu)
results in the overexpression of the HER2 protein (receptors) on the surface of
breast cancer cells.
• Medications that target HER2 include -
1.Herceptin, a monoclonal antibody, is given intravenously (IV), usually once a week or once
every three weeks. Side effects include fever and chills early on. Heart failure may develop in 3 to
5% (reversible)
2. Kadcyla (ado-trastuzumab): Kadcyla is combination of Herceptin and a very potent
chemotherapy drug (emtansine).
3. Perjeta (pertuzumab): , a monoclonal antibody
4. Tykerb (lapatinib):
5. Enhertu (trastuzumab deruxtecan)
6. Tukysa (tucatinib): combination of Herceptin and Xeloda (capecitabine)
7. Margenza (margetuximab):monoclonal antibody
Kinase inhibitors

• Kinases are molecules that help send growth signals in cancer cells. Kinase inhibitors
work by blocking the action of receptor tyrosine kinases
• Lapatinib (Tykerb):
• Neratinib (Nerlynx):
• Tucatinib (Tukysa):
Targeted therapy for hormone receptor-positive breast
cancer(cyclin-dependent kinases (CDKs)

• Palbociclib (Ibrance),
• ribociclib (Kisqali),
• abemaciclib (Verzenio)
Estrogen Receptor (ER)

• prognostic value, as well as biologic marker of response to treatment in breast cancer.

• Two activated forms
1.ERa homodimers: localized on human chromosome 6
2.ERp heterodimers: chromosome 14
• The greater the ER content of the tumor, the higher the response rate to endocreine
therapy.
• False-positive results of ER assays (ER-positive tumors but no response to endocrine
therapy) are more common than are false-negative results.
• (explanation is heterogeneity of tumor with biopsy of a site that is not representative )
SERM & SERD

• Tamoxifen
• acts like an anti-estrogen in breast cells, it acts like an estrogen in other tissues,
like the uterus and the bones.
• Toremifene (Fareston)
• Fulvestrant (Faslodex)
-selective estrogen receptor degrader (SERD)
-It acts like an anti-estrogen throughout the body. When given to pre-
menopausal women it must be combined with a luteinizing-hormone releasing
hormone (LHRH) agonist to turn off the ovaries
• Trastuzumab and hyaluronidase injection (Herceptin Hylecta) is given as a
subcutaneous shot.
• Pertuzumab (Perjeta): This HER2 monoclonal antibody ,I.V
• Trastuzumab, pertuzumab, and hyaluronidase injection (Phesgo): combination of
these drugs given as a subcutaneous.
• Margetuximab (Margenza):
CANCER GENOMICS PROFILING AND PRECISION MEDICINE