Aspirin for the primary prevention of breast cancer: an unforeseen advantage : IJS Global Health

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Editorial

Aspirin for the primary prevention of breast cancer: an unforeseen advantage

Sheikh, Ayesha MBBS*; Masood, Zainab MBBS; Abro, Khadija MBBS; Malik, Farheen MBBS; Ali, Eman MBBS

Author Information
International Journal of Surgery: Global Health 6(1):p e101, January 2023. | DOI: 10.1097/GH9.0000000000000101
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Breast cancer is the most prevalent type of cancer and the main reason for female cancer-related deaths worldwide. It has an annual incidence of about 2.3 million cases and 685,000 fatalities globally1. It is classified into 3 clinical subgroups based on biomarker subtyping: hormone receptor-positive (HR+), human epidermal growth factor receptor-positive (HER2+), and triple negative (TN)2. Modifiable risk factors include, but are not limited to obesity, inadequate vitamin intake, alcohol consumption, and sedentary lifestyles. Family history, exposure to high-dose radiation to the chest, genetic mutations, and advanced age are risk factors that cannot be changed3. The symptoms include lumps, pain, and abnormal breast shape, fatigue, breathlessness, neck, and back pain4.

Its progression is most likely the result of intricate interactions between multiple genes, estrogen, and inflammation-related variables5. Tumor growth often begins with ductal hyperproliferation and progresses to benign tumors or even metastatic carcinomas after being repeatedly activated by different carcinogens6. It is more likely to arise when either of the 2 well-known anti-oncogenes, breast cancer type 1 (BRCA1) or BRCA2, is mutated6. Its risk is also increased by gene mutations in checkpoint kinase 2 (CHEK2), partner and localizer of BRCA2 (PALB2), ataxia-telangiectasia mutated (ATM), RAD51C, RAD51D, BRCA1 associated ring domain 1 (BARD1), and tumor protein 53 (TP53)7. The overexpression of HER2 an important BC oncogene, which is detected in about 20% of BC patients, promotes cancer stem cell formation by signalling through phosphatase and tensin homolog (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin complex 1 (mTORC1) pathway8. The majority of tumors have biologically expressed estrogen and progesterone receptors, hormones known to drive the growth and proliferation of cancer cells. The COX-2 pathway produces prostaglandins by increasing the production of aromatase, which increases the amount of estrogen, thereby contributing to pathogenesis9.

There has been an increased focus on the role of aspirin as a chemopreventative drug. Recent studies have found that in addition to its anti-inflammatory and cardioprotective characteristics, it serves a role in modulating BC risk9. Its ability to prevent cancer is mediated by its ability to reduce cell proliferation, induce apoptosis, and modify lymphangiogenesis10. Although the precise method by which aspirin exerts its protective effects on BC is not entirely understood the fundamental mechanism could be explained by suppressing cyclooxygenases (COXs), particularly COX-2, whose overexpression is associated with lymph node metastases, larger tumor sizes, and worse prognoses10. COX-2 suppression inhibits prostaglandin synthesis, which lowers estrogen levels. Furthermore, cytochrome P450 aromatase, which is responsible for converting testosterone to estrogen, leading to increased estrogen synthesis in breast tissue adipose cells, is also blocked10,11.

Christopher Coyle administered daily doses of 100 mg of aspirin for around 8 weeks to 11,000 participants in his phase 3 randomized controlled trial. One of the important findings was the overall survival for the breast group, as well as the prostate, colorectal, and gastro-esophageal cohort12. A meta-analysis found that aspirin may reduce the overall risk of breast cancer in postmenopausal women, with data suggesting a significant reduction with relative risk of 0.92 (95% CI, 0.89–0.96; I2=72%)13. Recent double-blind randomized controlled clinical research suggests that low-dose aspirin 100 mg/d may lower estrogen levels in postmenopausal women and may be a good candidate for adjuvant therapy to lower the incidence of BC10. However, in contrast to these results, a phase III randomized, controlled clinical study found that consuming 300 mg of aspirin daily does not help prevent recurrence in persons with HER2-negative BC14. Currently a trial is ongoing in which scientists believe that aspirin’s anti-inflammatory properties could help combat aggressive triple negative BC by making tumors more sensitive to anti-cancer medications. The researchers anticipate that a satisfactory outcome from this trial will pave the way for novel therapeutic approaches15. Due to a limited follow-up period, a small sample size, and a lack of data on the precise frequency of usage or dose, it may not be feasible to evaluate an association between aspirin and a reduction in the risk of getting BC until more research has been conducted10.

Aspirin has recently emerged as a new target of cancer prevention and treatment research; yet, clinical investigations have yielded contradictory results about its anticancer properties13. It is an affordable, common medication that is widely accessible and might theoretically provide a cheap, low-risk mechanism of prevention. Its use as an adjuvant treatment would change if it was proven to be beneficial, even in little quantities. In contrast to multiple new treatments or difficult regimens like a regular follow-up, and the use of ionizing radiations, all of which have their own set of drawbacks and exorbitant costs, this intervention may be implemented quickly and extensively, even in nations with limited resources, and has the potential to drastically reduce the global burden of BC. Stroke, gastrointestinal bleeding, and allergic reaction are all possible side effects and problems of daily use. As a result, its usage is contraindicated in the case of a bleeding or clotting disease, allergy, bleeding stomach, or any major dental surgery in the future. As the incidence rate of BC is expected to climb further, research into effective preventative techniques, such as aspirin administration, could potentially prove to be a foundation of an interception strategy. More trials must be carried out to accurately assess the effectiveness of the treatment for all types of breast cancers because the trials were only focused on one particular type. Existing research suggests that aspirin may be able to lower the risk of BC. However, to study the greatest benefit-risk ratio, numerous, bigger multicenter, long-term prospective cohort studies, randomized controlled trials and meta-analyses are needed before a conclusive relationship and the ideal dose range, frequency, and duration of its use can be determined.

Ethical approval

None.

Sources of funding

None.

Author contribution

A.S.: conception of the study, drafting of work, final approval, and agreeing to the accuracy of the work. Z.M., K.A., F.M., and E.A.: drafting of work, final approval, and agreeing to the accuracy of the work.

Conflict of interest disclosures

None.

Research registration unique identifying number (UIN)

None.

Guarantor

None.

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Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of IJS Publishing Group Ltd.