Abstract
Triple-negative breast cancer (TNBC) is one of the aggressive subtypes of breast cancer that occurs in women. Unfortunately, the prognosis and management of TNBC pose great difficulty. However, a new study by the University of Texas M. D. Anderson Cancer Center reports an association between statin use and improved survival rates among TNBC affected individuals.
Triple-Negative Breast Cancer (TNBC)
TNBC is a subtype of breast cancer that lacks any receptors generally found in breast cancer cells. The other types of breast cancers have receptors for any of these hormones:
- Estrogen
- Progesterone
- Human Epidermal Growth Factor (HER2)
*Note: Receptors are proteins that receive chemical signals by binding to specific molecules.
TNBC represents about 10-15 % of all breast cancers.
The presence of even one of the receptors makes treating breast cancer easier. Doctors can then treat cancer by targeting these receptors to get inside the cancerous cell and destroy it.
However, in TNBC, the lack of receptors limits the treatment options.
According to the American Cancer Society, based on diagnosis information between 2010-2016, the 5-year survival rate for TNBC affected individuals is 77%. However, these statistics are subject to variation depending on the cancer progression stage and grade of the tumor.
Risk Factors for Triple-Negative Breast Cancer
- The most significant risk factor for TNBC is genetics. People having a BRCA mutation are at higher risk of developing TNBC. Almost 80% of BRCA mutations are triple-negative.
Know about your BRCA status and risk for breast cancer using Xcode Life’s BRCA and Breast Cancer Report.
- Women under the age of 40 years are at a higher risk, as are women in their premenopausal phase.
- Ethnicity and ancestry play a significant role in TNBC. For example, people from African American and Hispanic backgrounds are more likely to be diagnosed with TNBC.
- Socioeconomic status may also contribute to TNBC diagnosis. For example, a study reported that disparities in income levels and prejudiced healthcare facilities due to socioeconomic status prominently affected TNBC mortality.
- Among other body conditions, obesity is one of the most significant risk factors for TNBC. Therefore, the implication of obesity in TNBC prediction can be used to modify diet and lifestyle choices which will help prevent the development of TNBC.
What are statins?
Statins represent a class of drugs usually prescribed for heart attacks and stroke. Statins help in lowering blood cholesterol levels.
Statins can be broadly classified into lipophilic and hydrophilic statins. Lipophilic statins are fat-soluble, and hydrophilic are water-soluble.
- Lipophilic statins: Simvastatin, fluvastatin, pitavastatin, lovastatin, and atorvastatin
- Hydrophilic Statins: rosuvastatin and pravastatin
Notably, lipophilic statins quickly enter the cells and communicate with cell membranes. In contrast, hydrophilic statins show more selectivity to liver cells.
Explore your body’s response to different types of statins with Xcode Life’s Personalized Medicine report.
Statins & TNBC
The earliest research to report a link between statin and TNBC was a study in 2013. According to the study, statins activate the inhibition of TNBC through the PI3K pathway. They also suggested Simvastatin as a potent candidate for the treatment of TNBC, especially for wild-type (a form of the gene occurring naturally and predominating a population) expression of PTEN in the TNBC tumors.
Another study, done in 2017, to investigate the outcome of statin use on TNBC produced mixed results. The study observed no apparent association between statin use and overall survival (OS) in an unselected cohort of TNBC patients.
However, statin use significantly improved OS within a specific group of test subjects whose cholesterol and triglyceride levels were controlled. In addition, statin use showed a pronounced effect on survival rate even for another group of triple-negative patients who experienced metastatic failure.
*Note: 1. Overall survival: Length of time from the diagnosis date or start of treatment that a patient is still alive.
2. Metastasis: Stage of cancer where the cancerous cells start migrating from their origin site and infect other healthy parts of the body.
In 2019, a study found that the effect of statin use on breast cancer survival depended on the duration of statin use. In the test subject group, patients who had a medical history of statin use for more than five years experienced a conspicuous improvement in survival rate.
(NB: The findings of the study were irrespective of breast cancer type or receptor subtype)
In 2020, a statistical study on the clinical outcome of statin use on breast cancer diagnosis involving multiple research studies found a significant association between statin use and decreased recurrence rate and breast-cancer mortality in women.
| Year | Study | Outcome |
| 2013 | Statin induces inhibition of triple negative breast cancer (TNBC) cells via PI3K pathway. | Statin activates inhibition of TNBC through the PI3K pathway |
| 2017 | Impact of Statin Use on Outcomes in Triple Negative Breast Cancer. | Statin use improved survival rates in TNBC patients who:Had their cholesterol and triglyceride levels controlledExperienced metastatic failure |
| 2019 | Impact of long-term lipid-lowering therapy on clinical outcomes in breast cancer. | Long-term (>5 years) use of statin improved survival rates in TNBC patients |
| 2020 | Association Between Statin Use and Prognosis of Breast Cancer: A Meta-Analysis of Cohort Studies. | Significant link between statin use and decrease in the recurrence rate of TNBC and disease-specific mortality in women. |
The Study – Statins Can Improve Survival Rates for TNBC
A study led by Kevin Nead of the University of Texas M. D. Anderson Cancer Center explored the outcomes of statin use in breast cancer patients. This study was the first to investigate the effect of statin use on all subtypes of cancer, focusing mainly on TNBC.
According to Nead, “Previous research has looked at breast cancer as only one disease, but we know there are many subtypes of breast cancer, and we wanted to focus our research on this particularly aggressive form of breast cancer that has limited effective treatment options.”
Study Conditions
The study analyzed 23,192 female patient data included in the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry and the Texas Cancer Registry (TCR)-Medicare databases between 2008-2015. Patients were at least 66 years of age and diagnosed with stage I-III breast cancer.
2281 patients out of 23,192 were individuals who commenced statin use within 12 months of a breast cancer diagnosis. Out of these 2281 patients, 78.1% were white, 8.9% were black, 8.4% were Hispanic, and 4.5% belonged to other races.
The study also assessed the type-specific effect of statin on breast cancer outcomes.
Results of The Study
- In a specific TNBC subgroup of 1534 patients, statin use influenced a 58% relative improvement in breast cancer-specific survival (BCSS) rate and a 30% relative improvement in OS rate.
- In a specific TNBC subgroup of 1534 patients, statin use influenced a 58% relative improvement in breast cancer-specific survival (BCSS) rate and a 30% relative improvement in OS rate.
- In a specific TNBC subgroup of 1534 patients, statin use influenced a 58% relative improvement in breast cancer-specific survival (BCSS) rate and a 30% relative improvement in OS rate.
- In a specific TNBC subgroup of 1534 patients, statin use influenced a 58% relative improvement in breast cancer-specific survival (BCSS) rate and a 30% relative improvement in OS rate.
Let’s lower the risk of TNBC!
- Keeping a check on body weight and/or obesity, especially for women who have undergone menopause, can help in minimizing breast cancer risk.
- Adopting a Mediterranean diet and foods containing fiber over “Western-type” diets can help with reducing or managing obesity.
- Dietary patterns, including plant foods, legumes and/or fish and/or poultry, and unsaturated fats, are associated with a lower risk of cancers and youth mortality.
- Limiting alcohol consumption to 1 drink per day for women and two drinks per day for men or stopping alcohol consumption minimizes breast cancer risk.
- Cruciferous vegetables like broccoli, cauliflower, and Brussels sprout, and allium vegetables like onion and garlic can be included in the diet for their anti-cancer properties.
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Summary
- TNBC is the most aggressive of all breast cancers as it lacks all three receptors; it is, therefore, harder to diagnose and treat.
- Statins can help in prolonging lifespan by improving survival rates in TNBC.
- Long-term and high-intensity use of statins, predominantly lipophilic statins, increases the OS rate.
- The stage of cancer and tumor grade is essential to consider while looking at survival rates and statistics.
- Managing weight by judicious inclusion of dietary elements while cutting down on alcohol can help prevent breast cancer.
References
- https://doi.org/10.1002/cncr.33797
- https://www.cdc.gov/cancer/breast/triple-negative.htm
- https://www.cancer.org/cancer/breast-cancer/about/types-of-breast-cancer/triple-negative.html
- https://www.healthline.com/health/triple-negative-breast-cancer-outlook-survival-rates-stage
- https://www.sciencedirect.com/science/article/abs/pii/S0006291X13013697?via%3Dihub
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559964/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596255/
- https://www.cancer.org/healthy/eat-healthy-get-active/acs-guidelines-nutrition-physical-activity-cancer-prevention/guidelines.html
