Zometa® for Preventing Bone Loss Among Women on Endocrine Therapy for Breast Cancer

The majority of breast cancers are hormone receptor-positive. These cancers are stimulated to grow by the circulating female hormones estrogen and/or progesterone. Women with hormone receptor-positive breast cancer are often treated with endocrine therapy which increases their risk of bone loss. Early clinical trials suggest that Zometa can reduce the risk of bone loss in women being treated with endocrine therapy.²

Zometa is a bisphosphonate drug that is used for the treatment of cancer-related hypercalcemia (high levels of calcium in the blood) and of bone metastases in patients with advanced cancers. 

Femara is one type of endocrine (hormonal) therapy which is an estrogen-blocking drug that is commonly prescribed to postmenopausal women diagnosed with breast cancer. One side effect associated with endocrine therapy is a loss in bone density. This may lead to increased risk of bone fractures.  Zometa is  frequently given to women receiving endocrine to strengthen bones and prevent bone loss.

A multi-center study was designed to determine the optimal timing of treating women on endocrine therapy with Zometa. Should Zometa be used soon as they begin treatment with Femara or can it be started when a patient experiences a loss of bone density or a fracture. The study included 1,065 patients and participants received either immediate or delayed treatment with Zometa twice a year for five years. Researchers evaluated changes in bone mass by analyzing bone mineral density scores.

• Women receiving immediate treatment had an increase in their bone density compared with women who received delayed treatment; the latter group had a loss in bone density.
• After 12 months of follow-up, women who had received immediate treatment had a 5.7% advantage in bone density compared with women who received delayed treatment.
• Both treatment strategies were well tolerated with few serious side effects. Bone pain, the most frequent side effect, was more common among patients receiving immediate treatment.

After 12 months immediate treatment with Zometa^® was found to prevent bone loss in postmenopausal breast cancer patients receiving Femara^®.

Zometa in Premenopausal Women

Zometa may also reduce recurrences of hormone-positive breast cancer among premenopausal women. A Phase III clinical study evaluating Zometa among premenopausal women with hormone-positive breast cancer was conducted by the Austrian Breast & Colorectal Cancer Study Group Trial 12. Participants included 1,803 premenopausal women with Stages I-II hormone-positive breast cancer. Following surgery all patients were treated with hormonal therapy consisting of the gonadotropin-releasing hormone analog goserelin for ovarian suppression and either Arimidex or tamoxifen. In addition some patients were treated with Zometa, and the outcomes of these patients were directly compared with those not treated with Zometa. Treatment was continued for three years, with a median follow-up of five years. In all treatment groups, researchers evaluated disease-free survival, recurrence-free survival, overall survival, and bone-metastases-free survival^.5

• Compared with hormone therapy alone, the addition of Zometa improved disease-free survival by 36% and recurrence-free survival by 35%.
• Among patients treated with Zometa, there was a slight reduction in risk of death as well as the development of bone metastases.

Women were followed for roughly seven years and those treated with Zometa had a 28% reduction in risk of recurrence and a 36% reduction in risk of death. No women experienced osteonecrosis of the jaw (death of bone tissue in the jaw: a rare side effect of some bone drugs).⁶

These results suggest that Zometa may improve outcomes among selected women with early-stage breast cancer. Not all studies have found a benefit of Zometa in early-stage breast cancer, however, and the role of Zometa for this purpose remains uncertain. Further study may be necessary to truly determine the impact of the addition of Zometa to hormone therapy on overall survival and the risk of developing bone metastases.

When Zometa Stops Working

Studies suggest that switching to another bisphosphonate drug may relieve improve pain relief from bones metastases when Zometa stops working^.7

XGEVA – another choice for preventing bone loss with endocrine therapy.

Connect With Others for Support and information

CancerConnect was the first social network created for people with breast cancer. Founded by oncologists to support cancer patients and their caregivers, over 40 million individuals have accessed CancerConnect programs since 1997. CancerConnect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating breast cancer from others. Share your experience, ask a question, or start a conversation by posting on CancerConnect.

Reference: 

1. Bundred, N., Campbell, I., Davidson, N., et al. Effective inhibition of aromatase inhibitor associated bone loss by zoledronic acid in post menopausal women with early breast cancer receiving adjuvant letrozole. Cancer. 2008; 112(5):1001-1010.
2. Brufsky A, Harker W, Beck J, et al. Zoledronic acid effectively inhibits cancer treatment-induced bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: 12 mos BMD results of the Z-FAST trial. Proc Am Soc Clin Oncol . 2005;23:Abstract 533.
3. Aft R, Naughton M, Trinkaus K et al. Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial. Lancet Oncology[early online publication]. April 1, 2010.
4.  Gnant, M. et al. Efficacy of zoledronic acid in premenopausal women with breast cancer receiving adjuvant endocrine therapy – the ABCSG-12 trial. Presented at: the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill., 31 May – 2 June, 2008; Abstract LBA4.
5.  Gnant, M. et al. Efficacy of zoledronic acid in premenopausal women with breast cancer receiving adjuvant endocrine therapy – the ABCSG-12 trial. Presented at: the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill., 31 May – 2 June, 2008; Abstract LBA4.

6. Gnant M, Mlineritsch B, Luschin-Ebengreuth G et al. Long-term follow-up in ABCSG-12: significantly improved overall survival with adjuvant zoledronic acid in premenopausal patients with endocrine-receptor-positive early breast cancer. Presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. December 6-10, 2011. Abstract S1-2.

7. Clemons M, Dranitsaris G, Ooi W, et al. A phase II trial Evaluating The Palliative Benefit of Second-Line Zoledronic Acid in Breast Cancer Patients with Either a Skeletal Related Event (SRE) or Progressive Bone Metastases (BM) Despite Standard Bisphosphonate (BP) Therapy. Proceedings from the 28th San Antonio Breast Cancer Symposium. December 8-11, 2005. Abstract #1122.