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Oct 17, 2024 · Mutations in the phosphatidylinositol-3-kinase alpha isoform gene (PIK3CA) have been shown to be drivers of uncontrolled tumor growth, disease progression and resistance to endocrine-based...
- Overview
- What is the PIK3CA gene?
- PIK3CA mutation in metastatic breast cancer
- PIK3CA mutation-specific treatments
- Breakthroughs and clinical trials
- The outlook for people with a PIK3CA mutation
- The takeaway
PIK3CA is a gene that can contribute to the growth of breast, ovarian, colon, or brain cancer when mutated. A doctor can test you for this genetic mutation.
•A mutation in the PIK3CA gene can cause cells to divide and replicate uncontrollably. It contributes to the growth of many cancers, including metastatic breast cancer (MBC).
•If your tumor has a PIK3CA mutation, new treatments that specifically target this mutation could be used to treat your cancer.
•The Food and Drug Administration (FDA) has approved a treatment called alpelisib (Piqray) specifically for people with HR-positive and HER2-negative MBC whose tumors have a PIK3CA mutation.
If you’ve received a diagnosis of breast cancer and your cancer returns or doesn’t improve after initial treatment, your doctor will likely perform additional tests to help understand if and where the cancer has spread.
Tests can also identify specific genes, proteins, and other molecular factors unique to your tumor. Your doctor can use these test results to inform treatment decisions.
The PIK3CA gene holds the instructions for making a protein called p110 alpha (p110α). P110α has many functions in the body, including:
•cell growth and division
•cell movement
•producing proteins
•transport of materials in cells
•cell survival
Metastatic breast cancer (MBC), also known as stage 4 or advanced breast cancer, means that the cancer has traveled from the breast tissue, or metastasized, to other parts of the body, like the liver, lungs, or brain.
Survival rates are lower in advanced breast cancer, but the right treatment can improve both length and quality of life.
According to a 2018 study involving more than 10,000 people, genetic mutations like those found in PIK3CA aren’t as common in early stage breast cancers.
But when PIK3CA mutations do occur in these cases, their presence is often associated with better clinical outcomes.
Knowing your tumor type and mutation status can help your doctor decide which treatment or combination of treatments are likely to work best to treat your cancer.
A 2020 study in 649 people found that people with HR-positive, HER2-negative breast cancers and PIK3CA mutations are less sensitive, or resistant, to chemotherapy drugs, including paclitaxel, doxorubicin, and 5-fluorouracil.
This means that chemotherapy is less likely to help treat the cancer.
In 2019, the Food and Drug Administration (FDA) approved a treatment specifically for people with MBC whose tumors have a PIK3CA mutation. This drug, known as alpelisib (Piqray), is considered a “PI3K inhibitor.”
Piqray can be used in postmenopausal women and men with advanced breast cancer whose tumors have the PIK3CA mutation and are HR-positive and HER2-negative.
Piqray should be used in combination with a hormone treatment known as fulvestrant (Faslodex). Piqray is a tablet taken by mouth.
Alpelisib’s approval was based on the results of a clinical trial called the SOLAR-1 study.
The trial included 572 female and male participants with HR-positive and HER2-negative breast cancer who already tried treatment with an aromatase inhibitor, like anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin).
The study found that alpelisib significantly improved the amount of time people lived without their breast cancer getting worse. This is called progression-free survival.
The median progression-free survival was 11 months for people who received alpelisib plus fulvestrant. It was 5.7 months for people who received a placebo plus fulvestrant. This effect was stronger in people with a mutation in the PIK3CA gene.
Additional clinical trials are underway to assess new combinations of treatments involving alpelisib. These trials will also look at the role of similar gene mutations (for example, PIK3CA amplifications or PIK3R1 mutations) to better select people for this therapy.
There are also several other PIK3CA inhibitors under investigation in clinical trials in people with advanced breast cancer and a mutation in the PIK3CA gene, including taselisib and pictilisib.
Research suggests that recurrence-free survival may be better for people who have a PIK3CA mutation in their tumors compared with people who don’t have the mutation.
However, MBC is still difficult to treat. Many individual factors play a role in survival rates, including how well certain treatments work for your cancer type.
The approval of alpelisib (Piqray) means there’s now a targeted treatment for people with advanced breast cancer who have a PIK3CA mutation.
People who take alpelisib may live longer without their cancer progressing compared with people who have a PIK3CA mutation and don’t take this drug.
However, not all people with PIK3CA mutations experience the same benefits from treatment with a PI3K inhibitor like alpelisib.
More research is needed to determine the best treatments for people who don’t benefit from this type of treatment.
If you have MBC, knowing your PIK3CA gene status can be helpful if your cancer hasn’t improved or has come back after treatment, especially if you have HR-positive/HER2-negative breast cancer.
Ask your doctor if you should get tested for the mutation. If your test results are positive for a mutation in PIK3CA, newer treatments that specifically target it could help improve your outlook.
- Jacquelyn Cafasso
Jan 31, 2020 · Patients with PIK3CA- mutated triple-negative breast cancer (TNBC) present a better overall survival (OS). This could be explained by an enrichment of PIK3CA mutations in luminal breast cancer which lost HR expression in the metastatic setting.
Feb 2, 2024 · In a 2019 phase 3 clinical trial (SOLAR-1) published in the New England Journal of Medicine, the combination of Piqray and Faslodex (fulvestrant) almost doubled the progression-free survival rate of people with metastatic breast cancer positive for PIK3CA mutations from 5.7 months to 11.0 months.
Jul 11, 2023 · Citation, DOI, disclosures and article data. PIK3CA-related overgrowth spectrum (PROS) is a broad group of segmental overgrowth disorders that can occur with or without associated vascular anomalies, caused by activating mutations in the PIK3CA gene, which are also responsible for the vast majority of isolated lymphatic malformations and some ...
Dec 30, 2019 · Main signaling pathway initiated by growth factors that activate tyrosine kinase to initiate a series of downstream reactions that trigger P13K to generate second messenger (PIP3). PIP3...
People also ask
What is a PIK3CA mutation?
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Jul 15, 2022 · The Expert Panel determined that patients with locally recurrent unresectable or metastatic hormone receptor-positive and HER2-negative breast cancer who are candidates for a PI3K inhibitor, and a hormonal therapy should be tested for PIK3CA mutations.
