What is Bevacizumab?
Bevacizumab is a medication used in the treatment of certain types of cancers. It is sold under the brand name Avastin. This medication is often used along with chemotherapy to prevent further growth of the tumor cells.
Bevacizumab is known as an anti-vascular endothelial growth factor monoclonal antibody. Vascular Endothelial Growth Factor (VEGF) is a signaling protein that helps form blood vessels in the body. Blood supply is essential for cells to grow and multiply as it provides oxygen and nutrients. By acting as an anti-VEGF antibody, the medication starves the cancer cells and prevents their growth.
This is a biological medication (made from living organisms) approved by the US FDA (Food and Drug Administration). It is currently used as a first and second-line treatment option for colorectal cancers and as a first-line treatment option for non-small cell lung cancer.
Bevacizumab is also used to treat renal cell carcinoma, ovarian cancer, severe glioblastoma (tumor affecting the spine and brain), and advanced cervical cancer.
Bevacizumab In Breast Cancer Treatment
In 2008, the US FDA approved bevacizumab to treat metastatic (cancer that spreads from the primary location to other organs) HER2-negative breast cancer. In 2011 though, the FDA removed the medicine from the list of approved drugs for treating breast cancer.
According to the FDA, the potential side-effects and risks of this medication were much higher than its effect on breast cancer. They argued that bevacizumab only slightly increased the cancer-free period and did not increase the overall survival rate.
Though the medication has been removed from the approved drug list, doctors can still use it for breast cancer treatment with the patient’s approval.
How Does Bevacizumab Cause Hypertension?
There are many side effects of using Bevacizumab, and one such significant risk is bevacizumab-induced hypertension. Hypertension is consistently high blood pressure over 140/90.
Three theories explain how bevacizumab usage can cause hypertension.
Nitric Oxide (NO) Theory
NO is a molecule that is produced by almost all types of cells in the human body. NO helps the blood vessels relax and prevents high blood pressure. Studies show that reduced VEGF activity because of bevacizumab causes a decrease in the production of NO. Low NO levels lead to an increase in blood pressure.
Many experts support this theory because, in most patients, the blood pressure normalizes once they stop receiving Bevacizumab.
Kidney Impairment Theory
VEGF proteins are essential for the growth and maturation of the glomerular network in the kidneys. These are groups of small blood vessels located at the beginning of all the nephrons of the kidneys. The glomerular network filters the blood before it reaches the nephrons.
VEGF inhibition leads to abnormalities in the growth and maturation of the glomerular structure. This can lead to a condition called proteinuria. Proteinuria is the presence of excess proteins in urine.
Certain studies report that people with proteinuria have a higher risk of developing hypertension.
Pre-eclampsia-like Theory
Pre-eclampsia is a pregnancy complication that leads to high blood pressure. In pregnant women with pre-eclampsia, low VEGF levels are noted. As a result, this theory states that VEGF inhibition may be one reason for pre-eclampsia and, therefore, hypertension.
A 2010 meta-analysis published in the American Journal of Hypertension analyzed the relationship between bevacizumab therapy and hypertension. The analysis looked at 20 studies and a total of 12,656 cancer patients. According to the study, people treated with bevacizumab had a higher risk of developing high blood pressure.
Another meta-analysis studied the relationship between bevacizumab and hypertension in 72 clinical trials involving 21,900 patients. According to the study, 25.3% of these patients developed hypertension, and 8.2% had grade 3 and grade 4 hypertension.
A different meta-analysis analyzed the prevalence of hypertension in 3155 non-small cell lung cancer patients. The study reported that 19.55% of people developed hypertension after being treated with bevacizumab, and 6.95% developed high-grade hypertension.
How Does Genetics Influence Bevacizumab-induced Hypertension?
The SV2C Gene
The SV2C gene (Synaptic Vesicle Glycoprotein 2C gene) produces the SV2C protein. It plays a role in the normal functioning of the neural and endocrine cells and helps in low-frequency neurotransmission.
rs2059157 is a Single Nucleotide Polymorphism or SNP in the SV2C gene. The T allele of this SNP has been associated with an increased risk of bevacizumab-induced hypertension.
| Allele | Implications |
| T | Increased risk of bevacizumab-induced hypertension |
| C | Normal risk of bevacizumab-induced hypertension |
rs10051982 is an SNP in the SV2C gene. The A allele of this SNP has been associated with an increased risk of bevacizumab-induced hypertension.
| Allele | Implications |
| A | Increased risk of bevacizumab-induced hypertension |
| G | Normal risk of bevacizumab-induced hypertension |
Non-genetic Factors Influencing Hypertension During Chemotherapy
Bevacizumab Dosage
The effect of bevacizumab is dose-dependent. People who were treated with a higher dose of the medication (>10 mg/kg) had a 7.5-times higher risk for developing hypertension.
Age
People aged 60 and above have a higher risk of developing bevacizumab-induced hypertension when treated for cancer.
BMI Levels
People with BMI levels of 25 and above have a higher risk of developing bevacizumab-induced hypertension.
Pre Existing Hypertension
Those who have had high blood pressure before bevacizumab treatment are at a higher risk for developing high-grade bevacizumab-induced hypertension.
Type of Cancer
Among cancer patients who receive Bevacizumab, the risk of developing hypertension depends on the type of cancer. People with breast cancer or renal cell carcinoma show the highest risks for bevacizumab-induced hypertension.
Presence of other diseases
People with below pre-existing health conditions before bevacizumab treatment are at higher risk of developing hypertension during the treatment.
- Diabetes mellitus
- Renal (kidney) diseases
- High cholesterol levels
- Peripheral Artery Disease
- Obesity
Tips To Prevent/Manage Hypertension Due To Chemotherapy (In Breast Cancer)
Talk To Your Doctor To Get The Right Information
If your doctor suggests bevacizumab medication along with chemotherapy, then talk to your doctor to understand the risks associated with the drug. Understand how effective it could be to treat your breast cancer and if the benefits outweigh the risks.
Closely Monitor Your Blood Pressure Levels
The blood pressure starts rising from the first cycle of bevacizumab treatment. Make sure you closely monitor your levels at home and in a professional setup regularly. Talk to your doctor and opt for hypertension medications to prevent making the condition worse.
Manage Existing Hypertension Before Getting Treated For Breast Cancer
If you are already diagnosed with hypertension, make sure to stabilize your blood pressure levels before starting cancer therapy.
Start Antihypertensive Medications And Make Lifestyle Changes
Antihypertensive drugs help bring down blood pressure levels. It is recommended that you start on these along with your cancer treatment to prevent the risk of bevacizumab-induced hypertension. Make sure to consult a medical practitioner before getting started on any antihypertensives.
Some lifestyle changes can also help manage the condition.
- Lose weight
- Quit smoking
- Eat healthy foods
- Reduce sodium intake
- Reduce stress
- Limit caffeine intake
Opt For Genetic Testing
Genetic testing before opting for bevacizumab will tell you how risky you are for developing hypertension during cancer treatment. If you are a high-risk patient, mention this to your doctor so they can monitor your blood pressure levels more frequently.
Summary
- Bevacizumab is a medication used in the treatment of certain types of cancers. It is used along with chemotherapy to stop the growth of tumor cells.
- Though the FDA has currently removed bevacizumab from the list of approved medicines to treat breast cancer, doctors can still use it with the patient’s approval.
- Bevacizumab causes many side effects in cancer patients, including hypertension.
- Changes in some genes like the SV2C gene can increase the risk of developing bevacizumab-induced hypertension.
- The risk of developing hypertension increases with higher doses of bevacizumab. People aged 60 and above and those with BMI levels about 25 are at higher risk too.
- The prevalence of other diseases like diabetes mellitus, high cholesterol, kidney problems, and peripheral artery disease also increases the risk of bevacizumab-induced hypertension.
- Antihypertensive medications can help bring down the risk of high-grade hypertension. People undergoing bevacizumab therapy should regularly monitor blood pressure levels.
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