Statins confer some protection against breast cancer recurrence in Asians

Taking a statin after breast cancer surgery appears to reduce the risk of disease recurrence in Asians, especially among those with invasive cancers, as shown in a study from Singapore.

Among women with invasive diseases, statin use was associated with a lower risk of recurrence in the ER-positive (hazard ratio [HR], 0.57, 95 percent confidence interval [CI], 0.43–0.76; p<0.001), HER2-negative (HR, 0.74, 95 percent CI, 0.57–0.96; p=0.026), ER-positive/HER2-negative (HR 0.59, 95 percent CI, 0.43–0.80; p=0.001), and ER-positive/HER2-positive cancers (HR 0.46, 95 percent CI, 0.22–0.95; p=0.037), according to researchers from the National Cancer Centre Singapore.

They also noted that long-term statin use (≥6 years after surgery) reduced disease recurrence in all breast cancer subtypes (HR, 0.48; p=0.002), including ER-negative (HR, 0.34; p=0.036) and HER2-positive (HR, 0.10; p=0.002) invasive tumours.

Despite possible genetic differences in Asian breast cancer, pharmacokinetic differences in statin metabolism, and lifestyle difference, the findings suggested that statin use could help prevent recurrence after breast cancer treatment particularly in women with ER-positive and/or HER2-negative invasive diseases, the researchers said.

“This is similar to previous studies done in Europe and in the US that showed the beneficial effect of statins in reducing the risk of recurrence,” they added. [Lancet Oncol 2014;15:e461-468; J Clin Oncol 2017;35:1179-1188; Epidemiology 2015;26:68-78; BMC Cancer 2019;19:54; Breast Cancer Res Treat 2020;183:153-160]

The researchers specified several explanations why statins—HMG-CoA reductase inhibitors commonly used as cholesterol-lowering medications—can lower the risk of breast cancer recurrence. First, by lowering cholesterol levels, the drug helps inhibit oestrogen production as cholesterol modulates the action of oestrogen receptors. [Cancer Causes Control 2017;28:77-88; Front Endocrinol 2018;9:525]

Another reason is the possible synergism between statins and the adjuvant hormonal therapy (tamoxifen or an aromatase inhibitor). This has been demonstrated in in vitro studies where statins can work together with an aromatase inhibitor to induce cancer cell death by downregulating the expression of surviving proteins. [Breast Cancer Res Treat 2009;117:261-271; Mol Med Rep 2015;12:456-462; Breast Cancer Res Treat 2020;183:153-160]

Third, statins have a direct impact on the mevalonate pathway, which produces cholesterol, steroid hormones, and nonsteroid isoprenoids, which are necessary for cell survival, the researchers pointed out. [Exp Biol Med 2004;229:567-585]

With regard to the long-term recurrence risk-lowering benefit of statins, the researchers attributed this to the drug’s role in cancer dormancy.

“Tumour dormancy is a clinical phenomenon in which disseminated tumour cells remain occult, asymptomatic, and undetectable over a prolonged period of time. [It] contributes to local recurrence or distal metastasis up to years or decades after treatment. This may also explain why the protective role of statins in our ductal carcinoma in situ (DCIS) population is not appreciated. DCIS refers to the proliferation of neoplastic epithelial cells within the tubulolobular system of the breast… DCIS, by definition, is preinvasive (Stage 0) and has a much lower risk of recurrence than invasive cancer,” they explained. [Exp Hematol Oncol 2013;2:29]

The analysis included a total of 7,858 women with breast cancer, among whom 1,353 (17.2 percent) were statin users, with a median follow-up of 8.67 years. Statin use was defined as use after surgery, which helped remove the confounders of statin use duration, that statin use in itself may reduce breast cancer risk, and that statin users may have more favourable tumour characteristics and hence improved outcomes compared with nonusers.

“This is the first known retrospective study on the effect of statin use and breast cancer recurrence in an Asian population,” with some limitations including the fact that the vast majority of the patients were prescribed a lipophilic statin (96.3 percent) and the inability to adjust for body mass index and other lifestyle variables, according to the researchers.

“The risk reducing effects of statins on breast cancer recurrence, coupled with their cardioprotective effect, demonstrate the underlying complexity in cancer pathways and metabolism, and may open up new potential anticancer targets for future therapeutics,” they said.