Statins and breast cancer stage and mortality in the Women’s Health Initiative

Abstract

Purpose To evaluate the association between statins and breast cancer stage and mortality in the Women’s Health Initiative. Methods The study population included 128,675 post-menopausal women aged 50–79 years, out of which there were 7,883 newly diagnosed cases of in situ (19 %), local (61 %)-, regional (19 %)- and distant (1 %)-stage breast cancer and 401 deaths due to breast cancer after an average of 11.5 (SD = 3.7) years of follow-up. Stage was coded using SEER criteria and was stratified into early (in situ and local)- versus late (regional and distant)-stage disease. Information on statins and other risk factors were collected by self- and interviewer-administered questionnaires. Cause of death was based on medical record review. Multivariable-adjusted hazards ratios (HR) and 95 % confidence intervals (CIs) evaluating the relationship between statin use (at baseline only and in a time-dependent manner) and diagnosis of late-stage breast cancer and breast cancer-specific mortality were computed from Cox proportional hazards analyses after adjusting for appropriate confounders. Results Statins were used by 10,474 women (8 %) at baseline. In the multivariable-adjusted time-dependent model, use of lipophilic statins was associated with a reduction in diagnosis of late-stage breast cancer (HR 0.80, 95 % CI 0.64–0.98, p = 0.035) which was also significant among women with estrogen receptor-positive disease (HR 0.72, 95 % CI 0.56–0.93, p = 0.012). Breast cancer mortality was marginally lower in statin users compared with nonusers (HR 0.59, 95 % CI 0.32–1.06, p = 0.075). Conclusions Prior statin use is associated with lower breast cancer stage at diagnosis.

The relationship between statins and breast cancer prognosis varies by statin type and exposure time: a meta-analysis

“…The same result was confirmed by Gaia Pocobelli et al [3,4]. However, Pinkal Desai et al and Thunyarat Anothaisintawee found a lower hazard ratio of breast cancer for lipophilic statins than hydrophobic statins [5,6].…”

“…(1) On average, the deceased patients only accounted for a minority of the study population. In our study, the longest median followup time was 11.5 years in Pinkal Desai's study, which included 128,675 patients, although only 401 patients died from confirmed breast cancer [5]. The insufficient percentage of patients reaching this end point may dramatically affect the reliability of these results.…”

“…Two previous studies performed meta-analyses but suffered obvious limitations in terms of an insufficient number of included studies and the lack of unified end points [8,9]. Some articles have previously shown that different statin types may have different effects on breast cancer incidence [3][4][5] and prognosis [5,[10][11][12]19]. Thus, we preformed the current meta-analysis using mortality as the unified end point; moreover, we sought to explore the different influences of statin types and different follow-up times on the prognosis of breast cancer.…”

Statins and risk of breast cancer recurrence.

“…Statin use was found to be associated with increased overall DFS, in line with previous studies exploring the impact of statin use in breast cancer patients. 28,[33][34][35][36] Pre-or postdiagnosis statin studies have already shown a beneficial effect on survival 34,36 but not all of them. 28,33,35 Even in the latter case, where the studies showed no effect on survival, subgroups revealed any significant beneficial correlations; however, the number of patients in each subgroup was too small to draw definite conclusions, and the results should be interpreted with extreme caution.…”

The role of statins as therapeutic agents in cancer

“…In this regard, the results from different studies have been inconsistent. While some studies hint at a role of estrogen receptor status as a predictive biomarker for statin efficacy (Botteri et al 2013;Ahern et al 2014), others have found no such association (Desai et al 2015;Manthravadi et al 2016). Gray et al (2016) suggest that statin use appears to be associated with reduced mortality in colorectal cancer.…”