Zometa for Early-Stage Breast Cancer: Hormones May Matter

Can Zometa (zoledronic acid) prevent recurrence in women with early-stage breast cancer? Today we'll share the latest news and research. Links may be found on the Zometa (zoledronic acid) page of our website.

A new role for Zometa

Zometa is a bisphosphonate often prescribed to prevent bone loss in women taking aromatase inhibitors for breast cancer. It's also used to treat bone metastases in women with stage IV breast cancer.

Recent studies suggest Zometa may also prevent recurrence in women with early-stage breast cancer, but the results have been inconsistent. A new study in the New England Journal of Medicine suggests the key may lie in the hormonal status of the patient.

June: Zometa benefits premenopausal women on Zoladex and hormone therapy

A June 3 study in The Lancet Oncology evaluated Zometa in premenopausal women with hormone-receptor positive, stage I or II breast cancer, who were taking Zoladex (goserelin) for ovarian supression. (Drugs.com covered the study on June 3.)

About half of the 1,803 women took Zometa plus tamoxifen or Arimidex (anastrozole). The rest took tamoxifen or Arimidex alone.

At about 5 years follow-up, more than 2 years after completion of treatment with Zometa, 8% (76/900) of the Zometa group experienced a recurrence, compared to 12% (110/903) of the tamoxifen or Arimidex alone group. There was no significant difference in overall survival. (30 deaths out of 900 women taking Zometa, 43 out of 903 not taking Zometa.)

The authors concluded that the addition of Zometa "improved disease-free survival in the patients taking anastrozole or tamoxifen." They added, "These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer."

September: Zometa may only benefit postmenopausal women

In a September 25 New England Journal of Medicine study, about half of the 3,360 women with early-stage breast cancer were treated with Zometa plus standard chemo and hormone therapy. The rest received standard therapy alone. Patients varied in age, menopausal and hormone-receptor status.

In contrast to the Lancet study, at 5 years follow-up, the New England Journal of Medicine study found "no improvement" in disease-free survival for women with early-stage breast cancer taking Zometa. The authors concluded that their findings, "do not support the routine use of zoledronic acid as adjuvant therapy in unselected patients with early-stage breast cancer."

However, when the study participants were evaluated by subgroup, Zometa seemed to benefit postmenopausal women. (Reuters and Medical News Today covered this aspect of the study on September 25.) Zometa improved both disease-free survival (recurrence) rates and overall survival (death) rates for the group who had undergone menopause more than 5 years earlier.

The authors concluded, "For postmenopausal women, the use of bisphosphonates remains appropriate for the prevention of treatment-induced bone loss and osteoporosis and might have beneficial effects on disease outcomes. The optimum schedule, duration, and type of bisphosphonate therapy remain unknown."

Hormonal status may be the key

How do we reconcile these two studies? One found a benefit for premenopausal patients, the other did not. The answer may lie in the hormonal status of the patients.

The New England Journal of Medicine study noted that from a hormonal perspective, the postmenopausal patients in its study were similar to the premenopausal patients in the Lancet study who were treated with Zoladex for ovarian suppression. Both groups "had low levels of reproductive hormones at study entry." The authors suggest that Zometa "operates differently according to menopausal status."

Finally, the authors note that even though chemotherapy may induce menopause in young women, complete ovarian suppression may take "many months." They conclude, "Further investigation into the possible interaction between zoledronic acid and reproductive hormones is required."

At LATESTBreastCancer.com, we'll continue to follow developments in research on Zometa for breast cancer. We'll keep you posted.

Help for Women with Dense Breasts: U-Systems' somo-v Automated Breast Ultrasound (ABUS)

The movement toward enhanced breast screening for women with dense breast tissue is gaining momentum. Today's blog is meant to help these women advocate for a specific supplemental screening option: automated breast ultrasound. We'll focus on the somo-v ABUS system from U-Systems. I'll use a Q&A format.

First, how does Automated Breast Ultrasound (ABUS) differ from regular ultrasound?
Both use sound waves to detect abnormal structures in the breast that could be tumors. With plain vanilla ultrasound (hand-held ultrasound, or HHUS) either a radiologist or a highly-trained technician called a sonographer moves a kind of wand ("transducer") over the surface of the breast. Think of the wand like a flashlight. As the she moves the wand, she looks at the image on a monitor in real-time, trying to see possible tumors. Images can also be captured for later viewing.  With ABUS are that a much larger transducer is configured over the breast (it isn't manually moved over the breast), automatically taking different ultrasound images from different angles. These are then processed by a computer to construct a 3-D image.

What are the main advantages of ABUS?
First, the 3-D image gives a more complete picture of the entire breast than HHUS. Second, the images can be compared from year to year, or between visits, so any changes in the breast are easier to detect. Finally, the method doesn't require a diagnostic medical sonographer to perform. The imaging is automated, similar to mammography. So you don;t have to worry about whether or not the technician might be less experienced. Most ultrasound sonographers are trained and accredited. But their level of experience can also matter with HHUS.   

What systems are out there?
The main system on the market is called (and this is a mouthful...) the somo-v INSIGHT Automated Breast Ultrasound (ABUS) system.  It was developed by U-Systems, a Silicon Valley company that pioneered the field. A similar competing system called the ACUSON S2000 Automated Breast Volume Scanner (ABVS) is marketed by the large German company Seimens AG.

Can Automated Breast Ultrasound be used for screening?
The simple answer is "Yes, and it increasingly is." But realize that breast ultrasound, automated or not, is usually performed as a diagnostic procedure to further characterize a suspicious mammogram or MRI result. It's also commonly used to help surgeons guide needles when they perform biopsies.  Ultrasound is not traditionally used for screening to assess women with no suspicion of disease. However, given the growing concerns about mammography and women with dense breast tissue, ultrasound is increasingly used as a second, supplemental screening method for that subgroup of women. Generally, screening methods need to be more automated and require less technical skill than diagnostic methods, simply because more tests have to be performed more rapidly.  This is part of the appeal of the ABUS system.  But read on...

Is ABUS approved as a screening method in the US?
No. It's approved for diagnosis, but not for screening. That doesn't keep physicians from using it as a screening method. It does keep U-Systems from marketing it for screening. U-systems is conducting a very large study (20,000 women with dense breasts) in the United States to gain approval for screening. The study is looking at whether screening with mammography plus ABUS outperforms mammography alone.  Here we're talking about traditional 2-D mammography and not 3-D mammography (tomosynthesis). Enrollment continues, but the company already feels the data are strong and so they submitted an application to the FDA in April 2011. They added to the data a few weeks ago. The FDA could decide any day now.

Is ABUS approved as a screening method outside the US?
Yes, in Canada and in Europe. It was approved as a screening method by the Canadian regulatory agency Health Canada just last month (Aug 2011). Here's the announcement. It was granted European Union marketing approval a year ago (Sept 2010). Here's some info on that.

Is there a way I can see how it works?
The somo-v system was recently featured on Dr. Oz. Their site has three videos of that episode, which is all about supplemental breast screening. Watch all three if you have time.  If you just want to see the somo-v system, just watch part 2. Once you get there, you'll see the links to parts 1 and 3. Sorry but they're going to subject you to some commercials...

How much does it cost? 
That depends on the facility providing the service, but typically about $250-300.

Will it be covered by insurance?
That also depends on the judgment and policy of the facility you use, but often it's reimbursed.

How can I find a doctor that performs ABUS in my area?
First, you might check to see if you can get access through U-Systems' clinical study. Data from the trial have already been submitted, but they might still be recruiting. Outside of the clinical trial, it might take you a lot of time to call breast centers on your own. I'd probably just call the company (1-866-364-6777). Legally, remember, they can't talk about the system for screening. So just ask where there's a system installed in your area and hold the screening questions for the facility. Let's just call it "don't ask, don't tell!"


Where can I find more information?
Go to the somo-v Automated Breast Ultrasound page on the LATESTBreastCancer.com website. There we list web links to high-quality news articles and medical journal abstracts about every new medical option.

Afinitor, T-DM1 and Xeloda for Metastatic Breast Cancer

Today we'll share the latest news and research on Afinitor, T-DM1 and Xeloda for metastatic breast cancer.

Afinitor plus Aromasin (phase III)

The big story this week was a phase III trial of Afinitor (everolimus) plus Aromasin (exemestane) for post-menopausal women with advanced breast cancer presented at the 2011 European Multidisciplinary Cancer Congress (EMCC). Links to the EurekAlert!, Reuters and Bloomberg articles may be found on the Afinitor page of our website.

The trial, known as BOLERO 2, involved 724 hormone-receptor positive women whose cancer had become resistant to the aromatase inhibitors Femara (letrozole) or Arimidex (anastrazole). 485 received Afinitor plus Aromasin. 239 received Aromasin alone. Progression-free survival was almost 11 months in the Afinitor group, compared to about 4 months in the Aromasin alone group.

Afinitor is also being studied in combination with other drugs for advanced breast cancer. Novartis plans to file worldwide regulatory submissions for the Afinitor/Aromasin combination by the end of 2011.

TDM-1 (phase II)

Another EMCC presentation made headlines this week. The phase II study, TDM4450g, of trastuzumab emtansine (T-DM1) as first-line therapy in women with advanced HER2 positive breast cancer was covered by Medical News Today, Bloomberg and The Telegraph (UK).

The 137 patients were treated with either T-DM1 alone or Herceptin (trastuzumab) plus Taxotere (docetaxel). The median progression-free survival was 14.2 months with T-DM1 compared to 9.2 months with Herceptin plus Taxotere. In addition, the T-DM1 group suffered fewer side effects with less hair loss and hospitalization.

Larger, phase III trials are needed before regulatory approval. Last week, The Seattle Times shared an interesting story about Jeanne Sather, a breast cancer blogger whose efforts led to a geographic expansion of a T-DM1 trial. The story may be found on our T-DM1 page.

Navelbine/Gemzar vs. Xeloda alone (phase III)

Not all research on metastatic breast cancer involves brand new drugs. Some studies experiment with combinations of existing drugs.

A September 21 phase III study from Greece in the Annals of Oncology compared Navelbine (vinorelbine) plus Gemzar (gemcitabine) to oral Xeloda (capecitabine) alone for women with metastatic breast cancer previously treated with anthracyclines and taxanes.

Progression-free survival, overall survival and overall response were similar for both groups. The authors concluded, "Given the favorable toxicity and convenience of oral administration, single-agent capecitabine is recommended for compliant patients."

At LATESTBreastCancer.com, we'll continue to follow research on treatments for metastatic breast cancer. New developments will be added to our website and database and highlighted here. Please stay tuned.