BREAST CANCER

Adjuvant Zoledronic Acid: A New Standard of Care in Premenopausal Breast Cancer?
The first efficacy results from a randomized phase III trial (ABCSG-12) which evaluated adjuvant ovarian suppression using goserelin in combination with endocrine therapy (tamoxifen vs. anastrozole), alone or in combination with zoledronic acid (4 mg IV q 6 months), in premenopausal women (N=1,803) with endocrine-responsive early breast cancer (stage I/II) demonstrate that the addition of zoledronic acid to adjuvant endocrine therapy significantly prolonged the primary endpoint, disease-free survival (DFS), and relapse-free survival (RFS) compared to endocrine therapy alone. The risk of DFS events was decreased by 36% (HR=0.64, p=0.01) and the risk of RFS events was decreased by 35% (HR=0.65, p=0.015) for zoledronic acid vs. endocrine therapy alone. At a median follow-up of 5 years, the overall 5-year DFS is 94% and the 5-year OS is 98.2%. There was no difference in DFS or PFS between patients who received tamoxifen alone vs. anastrozole alone (p=0.59).

Conclusion: Adjuvant zoledronic acid improves clinical outcomes beyond those achieved by endocrine therapy alone, and has benefits beyond bone (reduction in contralateral breast cancer, locoregional recurrence, and distant non-bone recurrence) indicative of significant antitumor activity.
Abstract #LBA4 M. Gnant, et al. Plenary Session-J Clin Oncol 26: 2008

A “No-Chemo” Option for HER2+ Metastatic Breast Cancer?
Results of the largest study (296 patients) of two targeted agents, lapatinib (L) and trastuzumab (T), in HER2+ metastatic breast cancer (MBC) demonstrate the synergy of L+T and improved clinical outcome with the combination compared to L alone in heavily pretreated patients whose disease progressed on trastuzumab therapy. The primary endpoint was PFS and secondary endpoints were clinical benefit rate (CBR), RR, OS. The trial’s primary endpoint was reached; for PFS median was 8.1 weeks for L alone and 12.0 weeks for L+T (HR=0.73, p=0.008) with a 27% reduction in risk of progression despite prior treatment with multiple T regimens. PFS at 6 months 28% for L+T and 13% for L. For OS median 39.0 weeks for L vs. 51.6 for L+T (HR=0.75, p=0.106); 6 month OS 70% for L vs. 80% for L+T; 12 month OS 36% for L and 45% for L+T. CBR (CR+PR+SD ≥ 6 months) was 12.4% for L and 24.7% for L+T.

Conclusion: The numbers above demonstrate the synergy and the improved clinical outcomes, but the most exciting thing is that the total HER2 blockade with L+T has the potential to provide a chemotherapy-free option for treatment of HER2+ MBC.
Abstract #1015 J. O’Shaughnessy, et al. J Clin Oncol 26: 2008

Vitamin D Deficiency: A Negative Prognostic Factor in Early Breast Cancer?
Women with vitamin D deficiency at the time of breast cancer diagnosis are at increased risk of distant recurrence and death compared to women with normal vitamin D levels, according to the results of a prospective cohort study of 512 consecutive patients diagnosed with T1-3 N0-1, M0 breast cancer. Vitamin D deficiency was found in 37.5% and insufficient levels were found in 38.5% of patients, therefore only 24% had sufficient vitamin D levels. Low vitamin D levels were associated with premenopausal status, high body mass index (BMI), high insulin levels, and high tumor grade (all with p<0.03). Distant DFS (DDFS) was significantly worse in those with deficient levels of vitamin D (HR=1.94, p=0.02) as was OS (HR=1.73, p=0.02). Vitamin D associations with OS were absent in ER negative breast cancer patients.

Conclusion: Vitamin D deficiency is common at breast cancer diagnosis and predicts a poor outcome for these patients, but should we now obtain vitamin D and insulin levels on all newly diagnosed premenopausal patients?
Abstract #511 P.J. Goodwin, et al. J Clin Oncol 26: 2008

BMD Loss Secondary to Chemotherapy-Induced Ovarian Failure: What Can Be Done?
CALGB trial 79809 evaluated the effect of zoledronic acid (ZA) on bone mineral density (BMD) in premenopausal women who develop ovarian failure due to adjuvant chemotherapy. The trial compared the effect of early ZA (begun with adjuvant chemo) or late ZA (one year after chemo) on change in BMD in the lumbar spine (LS). The primary endpoint was bone loss (percentage change in BMD) at 12 months. 439 patients (median age 47) were randomized to receive ZA q 3 months for 2 years or no ZA (controls). All patients were told to take vitamin D and calcium. Results of the first interim analysis: 38% of patients had ovarian failure at 12 months. Majority of ZA-related toxicity was grade 1-2. The mean percentage change in BMD in the spine from baseline to 12 months was a 2.2% increase in the ZA patients compared to a 6.6% decrease (ie a “bone loss”) in the control arm patients.

Conclusion: Zoledronic acid prevented bone loss with no added toxicity when administered every 3 months. Given the impressive efficacy results the ABCSG-12 trial achieved using ZA q 6 months, was the q 3 month ZA regimen in this trial the best choice?
Abstract #512 C.L. Shapiro, et al. J Clin Oncol 26: 2008