How Can Molecular Testing Be Used in Breast Cancer?
- Breast cancer treatment is evolving and becoming more customized, targeted, and effective, in no small part due to molecular testing.
- Estrogen (ER), progesterone (PR), and HER2 receptor testing is routinely performed to guide treatment for all new diagnoses of breast cancers.
- Germline mutation testing — which evaluates the presence of mutations in BRCA1, BRCA2, PALB2, CDH1, PTEN, and TP53 genes — can also be performed to customize treatment options further.
- In patients with metastatic hormone-receptor-positive cancers, testing for the PIK3CA mutation can be performed to evaluate eligibility for new agents that can specifically target this mutation.
Oncologists nowadays use molecular profiling to determine the best treatment option for any particular patient. This technique analyzes the molecular characteristics of a patient’s breast cancer cells, generating a molecular profile that can then be used to pick the best treatment strategy.
What does ‘molecular profiling’ mean?
Read MoreHormone Receptor Testing
“The first thing that every breast cancer patient gets tested is their estrogen [ER], progesterone [PR], and HER2 [receptor status],” says Dr. Ankit Madan, a medical oncologist and hematologist at MedStar Health in Washington, D.C. ER and PR hormone receptor status helps determine how sensitive tumors are to the hormones: estrogen and progesterone. Should the tumors be sensitive to these two hormones, blocking them through hormone therapies, with drugs like tamoxifen (ER blocker), can help deter cancer growth. Additionally, the presence of these receptors can indicate a disease that will usually lead to better outcomes than cancers without these receptors.Similarly, HER2 is a protein present on many breast cancer cells and can drive their growth. If cancers express or over-express HER2 (termed HER2+), they can be candidates for drugs like trastuzumab (brand name Herceptin), pertuzumab (brand name Perjeta), and ado-trastuzumab emtansine (brand name Kadcyla) that specifically target HER2+ cells, inhibiting their growth and reducing the risk of recurrence.
Germline Testing
“[Another] test that we can use is germline [testing],” says Dr. Madan. Germline testing, which can be done via a saliva sample, cheek swab, or blood draw, looks at the genetic makeup or the DNA of germline cells for mutations that can drive cancer growth.
Germline cells are the cells responsible for passing genetic information from generation to generation, such as those that produce eggs and sperm in human beings. They are different from somatic cells, which are the non-reproductive cells that do not carry or transmit genetic information between generations.
Germline mutations predispose not only individuals but also their offspring to certain cancers.
BRCA1 and BRCA2 genetic mutations are the most well-known components of germline testing. The BRCA genes are tumor suppressor genes responsible for repairing damaged DNA, which is essential to normal cellular function.
Mutations in these genes can significantly increase the risk of developing certain cancers, including breast and ovarian cancers. The presence of these mutations can make patients eligible for specific therapies, including poly(ADP-ribose) polymerase (PARP) inhibitors, like olaparib (brand name Lynpraza).
PALB2 mutation is another commonly included mutation in germline testing. Like the BRCA genes, the PALB2 gene is involved in DNA repair, and mutations may be present in patients with breast cancers, particularly in individuals with a family history of the disease. While it can be present individually, this mutation can also occur with BRCA mutations, causing a double-fold paralysis of the DNA repair machinery.
“[Like the BRCA mutations], PALB2 mutation is another indication for using PARP inhibitors,” notes Dr. Madan.
Other targets of germline testing include CDH1, PTEN, and TP53. Although targeted therapies for such mutations are still in the investigative phase and not routinely used in clinics, their presence can indicate a more aggressive cancer requiring more aggressive traditional therapies.
PIK3CA Mutation Testing
The PIK3CA gene encodes part of an enzyme, and mutations in this gene are associated with aberrant activation of the PI3K pathway, which can lead to many cancers, including breast cancer. These mutations are frequently observed in hormone receptor-positive and HER2- breast cancers.
Expounding on PIK3CA mutation testing, Dr. Madan says, “[for] stage four breast cancer patients with hormone receptor-positive tumors, we typically test for PIK3CM mutation, as these patients may be eligible for a medication called Alpelisib.”
Alpelisib (brand name Piqray) is a targeted inhibitor of the alpha isoform of phosphoinositide 3-kinase (PI3Kα) encoded by the PIK3CA gene. By inhibiting PI3Kα, Alpelisib aims to block the aberrant activation of the PI3K pathway in cancer cells, preventing their proliferation.
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