Abstract P6-09-03: Improved clinical outcomes associated with statin use during adjuvant chemotherapy in patients with HER2+ non-metastatic breast cancer
Authors: Zeichner SB , Shah NN , Montero AJ , Gluck S , Ahn E 
Published: August 2014

Background

Statins are established as first line therapy in patients with hypercholesterolemia and are thought to have pleiotropic effects including inhibition of signaling pathways known to drive cell proliferation and survival responses. Numerous preclinical and observational studies have demonstrated activity and improved outcomes in breast cancer patients who received statins, particularly lipophilic statins, as part of their adjuvant therapy. In the Life After Cancer Epidemiology (LACE) Study, 1,945 early-stage breast cancer survivors were shown to have a 33% decreased risk of breast cancer recurrence with post-diagnosis statin use, an effect that was magnified with increasing duration of statin use. We hypothesized that statin use concurrent with trastuzumab based chemotherapy in patients treated for non-metastatic HER2 positive breast cancer would be associated with improved outcomes.

Methods

We performed a retrospective review of all patients (n = 300) with HER2+ breast cancer who received trastuzumab from 2006-2012 at UM/SCCC. We identified two groups of patients for comparison - those who received statins (ST) during adjuvant chemotherapy (n = 45) or no statins during chemotherapy (NST) during adjuvant chemotherapy (n = 200). Patients with unclear documentation of concurrent statin use, men, patients with de-novo-metastatic breast cancer or prior primary cancer, bilateral breast cancers, and patients without follow-up were excluded. 5-year disease free (DFS) and overall survival (OS) were calculated. A univariate analysis was performed. Multivariate analysis for time-to-event data, using the Cox and extended Cox regression model will be performed and reported.

Results

The median age at diagnosis was 58 and 48, in the ST and NST groups, respectively. The most commonly used statin was lipophilic simvastatin (34.1%). The average baseline and post chemotherapy total cholesterol level in the ST group was 200.8 and 218.1mg/dL, respectively. Descriptive characteristics of the ST and NST groups respectively are as follows: postmenopausal (77.8% vs. 43.5%) tumor size &lt;2cm (48.9% vs. 41.0%), node-negative disease (40.0% vs. 40.0%), HR+ status (64.4% vs. 60.5%), diabetes mellitus (26.7% vs. 9.0%), baseline BMI &gt;30 (40.0% vs. 27.0%), and concomitant metformin (28.9% vs. 11.5%). The NST group was more likely to have a reduction of greater than 10% in their EF (9.0% vs. 6.7%). At a median follow-up of 32 and 26 months, the estimated 5-year DFS was significantly improved in the ST group (81.8% vs. 51.5%, p = 0.046). Meanwhile, the estimated 5-year OS was not significantly different between both groups (93.4% vs. 91.6%, p = 0.121). Metformin was not associated with a significant improvement in DFS or OS.

Conclusion

Our study demonstrated that statin use concurrent with trastuzumab-based chemotherapy for non-metastatic HER2 breast cancer was associated with improved estimated 5-year DFS, but not OS. The retrospective nature of our study does not allow for a definitive answer but further research needs to be done to define the role of statins in HER2+ breast cancer treatment.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-03.