Statins could reduce breast cancer mortality by a fifth

Statins could reduce breast cancer mortality by a fifth

A new analysis of nearly 700,000 cases of breast cancer shows that statins can significantly improve patient outcomes and may challenge previous beliefs about their limited role in cancer treatment.

Study:Statin use and breast cancer-specific mortality and recurrence: a systematic review and meta-analysis including the role of immortal time biases and tumor characteristics. Photo credit: Maria sbytova/Shutterstock.com

A study published inThe British Journal of Cancer of Natureexamined the role of statins in breast cancer mortality and recurrence.

introduction

Breast cancer is the most common cancer and the cause of cancer-related deaths in women. Older women at higher risk often have cardiovascular risk factors and are therefore prescribed medications to mitigate them such as statins for high blood lipids.

Previous research suggests that statins are associated with reduced breast cancer recurrence and mortality. However, the observed associations between breast cancer recurrence or mortality and risk factors could depend on certain factors such as: E.g. immortal time distortions (ITB), estrogen receptor status or cancer stage. These could alter the size and direction of observed associations in previous meta-analyses without adjustment.

ITB refers to periods when an event such as death may not have occurred but is incorrectly counted as part of the time a patient was exposed to treatment. For example, if a woman was prescribed statins after her breast cancer diagnosis, she must have survived until the prescription date, so using the time before the prescription as “statin use” would falsely inflate the survival time. Additionally, the stage of cancer may affect how beneficial statins are.

The current paper is the first meta-analysis to systematically evaluate such effect modifiers. In addition to the assessments already mentioned, it also assesses the effects of the time of statin introduction (newly prescribed versus already used by the patient) and the type of statin.

Statin actions

In addition to inhibiting a key enzyme in the cholesterol synthesis pathway, statins also affect the cell cycle, suppressing proliferation and inducing apoptosis. They also influence immune responses. Finally, the enzyme they inhibit is overexpressed in breast cancers.

Animal and cell culture studies demonstrated the antitumor effects of statins. This led to several observational studies and meta-analyses, most of which showed that statins improve the prognosis of breast cancer.

About the study

The current study aimed to update these meta-analyses by including newer or missing studies and adjusting effect modifiers.

The analysis included 34 studies, including 689,990 women with breast cancer. Of these, 21 and 20 focused on death and recurrence of breast cancer as outcomes. All studies except two were adjusted for age-related differences in mortality.

Most studies adjusted for cancer stage and the presence of other diseases, but only about half adjusted for the use of different medications. Follow-up times of up to five years and 5-10 years were reported after 16 and 14 studies, respectively.

While 27 studies were considered non-ITB and 27 examined statin use after breast cancer diagnosis, five looked at their use before diagnosis and two included both periods. Lipophilic and hydrophilic statins were considered separately in 14 studies. Five studies stratified patients at the cancer stage, but 21 included only early-stage patients. Most studies were retrospective cohort studies with only five prospectuses in design.

Study results

The results show that statin use was associated with a reduced risk of breast cancer death by about 20%. Similar effects were found for recurrences.

Lipophilic statins had a more protective effect than hydrophilic statins against death, but not against death, but a finding that reflects preclinical studies showing the anti-proliferative effects of statins on breast cancer cells.

Differences in results by subgroup were not statistically significant. This contradicts previous studies that suggest, for example, statins are more effective in advanced breast cancer. Notably, in the current study, there were only a few studies that included advanced-stage patients, two of which showed a protective effect in early-stage patients. Future studies are needed to validate this finding.

There was a suggestion of a protective association in studies of ITB for breast cancer recurrence, but overall ITB did not appear to significantly bias the main pooled estimates. Similarly, the association for recurrence appeared to be stronger in estrogen receptor positive (ER+) patients, consistent with previous findings.

Small studies reported a significant reduction in breast cancer recurrence risk with statins, the “small trial effect.” This is primarily due to a few outlier studies that showed significant protective effects associated with statin use. However, funnel plot analysis and Egger's test were used to assess publication bias, and trim and fill analysis showed that protective association remained significant even after accounting for potential bias. Statin use appeared to protect against breast cancer recurrence by an estimated 24%.

Conclusions

“Statin use, particularly lipophilic statin use, was associated with favorable outcomes for BCD and BCR. "" The current study is consistent with almost all previous analyzes of the protective effects of statins on breast cancer mortality and recurrence rates.

This is the first meta-analysis to comprehensively evaluate effect modifiers such as ITB and timing of use after diagnosing statin. There was no significant difference in association with either outcome in ITB studies compared to those not at risk for ITB. Similarly, statin use initiated after breast cancer diagnosis was not significantly associated with a reduction in death or recurrence rates. However, it narrowly missed the threshold for significance in the case of recurrences.

The wide variation in methodology, study criteria and results between studies makes it difficult to understand whether the protective effects are due to statins or other factors independent or combined with statin use such as cardiovascular disease that predict higher mortality. Further research is needed to identify specific subgroups of patients who may benefit from statins as adjuvants for cancer treatment.

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