News from the 33rd Annual San Antonio Breast Cancer Symposium

Breast cancer researchers gather to share important advances in our understanding of an all-too-common disease.

By Kari Bohlke, ScD

Many Women Do Not Get Regular Mammograms

Despite professional recommendations and public support in favor of regular mammography, only about half of US women get an annual mammogram, even if they have insurance to cover the test.1

To determine mammography rates, researchers reviewed a database of more than 12 million people. Information was collected about screening mammograms that took place between January 2006 and December 2009. All participants had employer-provided insurance or were on Medicare.

In any given year, only 50 percent of women age 40 to 85 years had a mammogram. Though this study did not investigate reasons why women may not get mammograms, it has been thought that discomfort from mammography and lack of available screening centers may be among the reasons why some women do not undergo this screening.

Zometa Fails to Reduce Recurrence of Early Breast Cancer

Among women with early breast cancer, adjuvant (post-surgery) use of Zometa® (zoledronic acid) did not reduce the risk of cancer recurrence.

Zometa is a bisphosphonate drug that is used for the treatment of cancer-related hypercalcemia (high levels of calcium in the blood) and to reduce bone complications from multiple myeloma or bone metastases. Some research has suggested that Zometa may also have anticancer effects.

To evaluate the effects of Zometa among women with early breast cancer, researchers conducted a Phase III clinical trial known as AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence).2 Study participants received standard cancer treatment alone or in combination with Zometa.

Overall, Zometa did not improve disease-free survival. In the subset of women who were at least five years beyond menopause, however, Zometa improved overall survival by 29 percent.

These results do not support the routine use of Zometa to improve cancer outcomes among women with early-stage breast cancer. The possibility that Zometa may benefit postmenopausal women with early breast cancer warrants additional research.

Combination of HER2-Targeted Therapies May Provide Breast Cancer Benefit

Among women with early, HER2-positive breast cancer, treatment with a combination of HER2-targeted therapies may produce better outcomes than treatment with a single HER2-targeted therapy. This was the conclusion of two studies presented at San Antonio.

Approximately 20 to 25 percent of breast cancers overexpress (make too much of) a protein known as HER2. Drugs that target HER2 have improved outcomes for women with HER2-positive breast cancer. These drugs include Herceptin® (trastuzumab), Tykerb® (lapatinib), and the investigational drug pertuzumab.

The NeoALTTO study is a Phase III clinical trial that enrolled women with early, HER2-positive breast cancer.3 The results indicated that neoadjuvant (before surgery) treatment with chemotherapy plus a combination of Tykerb and Herceptin produced higher response rates than chemotherapy plus Tykerb or Herceptin alone.

A second study—the Phase II NeoSphere study—evaluated the combination of Herceptin and pertuzumab among women with early HER2-positive breast cancer.4 Once again neoadjuvant treatment with chemotherapy plus a combination of HER2-targeted drugs produced the highest response rate.

Together these studies suggest that a combination of HER2-targeted therapies may be more effective than a single HER2-targeted therapy in the treatment of early breast cancer.

Higher Co-Payments May Limit Use of Breast Cancer Therapy

It appears that women with early breast cancer who are prescribed treatment with aromatase inhibitors (hormonal therapy drugs) are more likely to discontinue or not follow through with this therapy if insurance copayments are high.5 Among older women (over the age of 65), even fairly modest co-payments were linked with an increased likelihood of discontinuing therapy.

Because aromatase inhibitors can be highly effective, the researchers suggest “future public policy efforts should be directed towards reducing financial constraints as a means of increasing the complete use of these medications.”

Xgeva Delays Bone Complications in Women with Metastatic Breast Cancer

In a study of women with bone metastases from breast cancer, Xgeva™ (denosumab) delayed bone complications for five months longer than Zometa® (zoledronic acid).6

Several types of cancer—including breast cancer—have a tendency to spread to the bone. Bone metastases can lead to serious problems such as fracture and spinal cord compression and may require treatment with surgery or radiation therapy.

Xgeva was recently approved for the prevention of bone complications such as fracture in patients with bone metastases from solid (not blood-related) cancers.

To directly compare Xgeva with another bone drug—Zometa—researchers conducted a Phase III clinical trial among more than 2,000 patients.

Patients treated with Xgeva remained free of bone complications for a median of five months longer than patients treated with Zometa. Overall survival was similar in the two groups.

Circulating Tumor Cells Linked with Recurrence of Early Breast Cancer

Among women with early breast cancer, the presence of circulating tumor cells (cancer cells in the bloodstream) increases the risk of cancer recurrence and death.7

Circulating tumor cells have been linked with worse outcomes among women with metastatic breast cancer. To evaluate the significance of circulating tumor cells among women with early breast cancer, researchers evaluated more than 2,000 patients. The test to detect circulating tumor cells was performed after surgery and before the start of chemotherapy.

Circulating tumor cells were detected in 21.5 percent of patients. Compared with women with no circulating tumor cells, women with 1 to 4 circulating tumor cells were almost twice as likely to experience cancer recurrence and death. The presence of 5 or more circulating tumor cells was linked with a fourfold increase in recurrence risk and a threefold increase in risk of death.

These results suggest that detection of circulating tumor cells may provide information about recurrence risk and prognosis among women with early breast cancer. Studies to further evaluate the role of circulating tumor cells are under way.

Avastin Fails to Show Benefit in Early Breast Cancer

The addition of the targeted drug Avastin® (bevacizumab) to chemotherapy did not improve outcomes among women with early breast cancer.8

Avastin is a targeted therapy that blocks a protein known as the vascular endothelial growth factor (VEGF). VEGF plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Avastin has been approved for the treatment of selected patients with breast cancer, lung cancer, colorectal cancer, kidney cancer, or glioblastoma. As of this writing, the Food and Drug Administration announced that it had begun the process to remove approval of Avastin for breast cancer due to lack of clear evidence that the drug was safe and effective for this use. 9

To evaluate Avastin among women with early-stage breast cancer, researchers conducted a Phase III clinical trial (the GeparQuintolstudy) among 1,948 patients with HER2-negative breast cancer. Patients received neoadjuvant (before surgery) treatment with chemotherapy alone or in combination with Avastin.

The addition of Avastin did not improve response rate or rate of breast conservation, but did increase side effects. In the subset of women with triple-negative breast cancer (breast cancer that is estrogen receptor-negative, progesterone receptor-negative, and HER2-negative), there was a suggestion of a benefit from Avastin.

Overall, these results do not support the use of Avastin among women with early breast cancer. It’s possible that certain subgroups of breast cancer patients will benefit from Avastin, and researchers will continue to explore this question.

Aromatase Inhibitors May Increase Risk of Heart Disease

Aromatase inhibitors—hormonal therapy drugs commonly used in the treatment of postmenopausal breast cancer—may increase the risk of heart disease.

Hormonal therapy for breast cancer may involve tamoxifen, an aromatase inhibitor, or both in sequence. Both types of drugs slow or stop breast cancer growth by reducing the effects of estrogen on the breast. In postmenopausal women, studies have suggested that aromatase inhibitors are more effective than tamoxifen at reducing the risk of breast cancer recurrence.

Adverse effects of tamoxifen and aromatase inhibitors differ. Blood clots and endometrial (uterine) cancer are more common with tamoxifen, and bone loss is more common with aromatase inhibitors. Previous studies have also raised questions about the effects of aromatase inhibitors on the heart.

To further evaluate the issue of heart problems, researchers collected information from seven large clinical trials that compared tamoxifen with an aromatase inhibitor among postmenopausal breast cancer patients. 10

Compared with tamoxifen, use of an aromatase inhibitor was linked with a 26 percent increase in risk of heart disease. This is not a large increase in risk, but the researchers speculate that the risk may be greater for women who have other risk factors for heart disease.

Estrogen Alone May Reduce Breast Cancer Risk in Certain Women

Among women at low risk of breast cancer, postmenopausal hormone therapy with estrogen alone may reduce the risk of breast cancer. These results—which warrant additional research and should not be considered conclusive—came from further review of the Women’s Health Initiative (WHI) clinical trial of estrogen alone.

Hormone therapy with estrogen (with or without progestin) effectively manages many menopausal symptoms, but studies over the past several years have raised concerns about the health effects of postmenopausal hormone therapy. In the WHI clinical trial of estrogen plus progestin, hormone use decreased the risks of fracture and colorectal cancer, but increased the risks of heart disease, breast cancer, stroke, and blood clots.11 More recent reports suggest that combined hormone therapy may also increase lung cancer mortality.12 In the trial of estrogen alone, estrogen did not appear to increase the risk of breast or lung cancer, but did increase risk of stroke.13 Because estrogen alone increases the risk of endometrial (uterine) cancer, it is generally reserved for women who have had a hysterectomy.

In the analysis presented at San Antonio, researchers evaluated subgroups of women enrolled in the WHI trial of estrogen alone.14 In the subgroups of women at low risk of breast cancer (women without a strong family history of breast cancer and women without a personal history of breast disease), use of estrogen alone was linked with a reduced risk of breast cancer.

Although these results are intriguing, further research is required before firm conclusions can be drawn about the relationship between estrogen alone and risk of breast cancer.

Onco type DX Influences Breast Cancer Treatment Decisions

The Oncotype DX® breast cancer test may change treatment decisions for more than one-third of women with early, estrogen receptor-positive breast cancer.15

The Oncotype DX breast cancer test measures the expression of 21 genes in a sample of tumor tissue. The test generates a Recurrence Score® that provides information about the likelihood of cancer recurrence and the likelihood of chemotherapy benefit in women with early-stage, estrogen receptor-positive breast cancer.

Previous studies have indicated that use of the Oncotype DX breast cancer test can influence breast cancer treatment decisions. Test results may, for example, change the treatment recommendation from chemotherapy plus hormonal therapy to hormonal therapy alone (or vice versa).

To provide additional information about the impact of Oncotype DX on breast cancer treatment decisions, researchers combined information from seven studies.

Physicians who used Oncotype DX changed their treatment decisions for more than one-third of patients. Overall, there was a 28 percent reduction in the use of chemotherapy as a result of the test. Some women, however, had chemotherapy added as a result of their Oncotype DX test results. These women were initially considered low risk, but were reclassified as high risk based on their Recurrence Scores.

These results provide additional evidence that Oncotype DX can play an important role in treatment decisions for early breast cancer.

References

1. Subar M, Lust SA, Lin W. Compliance with mammographic screening guidelines from an administrative claims database. Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract S4-7.

2. Coleman RE, Thorpe HC, Cameron D, et al. Adjuvant treatment with zoledronic acid in Stage II/II breast cancer. The AZURE Trial (BIG 01/04). Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract S4-5.

3. Baselga J, Bradbury I, Eidtmann H, et al. First results of the NeoALTTO Trial (BIG 01-06/EGF 106903): a Phase III, randomized, open label, neoadjuvant study of lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2-positive primary breast cancer. Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract S3-3.

4. Gianni L, Pienkowski T, Im Y-H, et al. Neoadjuvant pertuzumab (P) and trastuzumab (H): antitumor and safety analysis of a randomized Phase II study (“NeoSphere”). Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract S3-2.

5. Hershman DL, Neugut AI, Subar M, et al. Association between prescription co-payment amount and compliance with adjuvant aromatase inhibitor therapy in women with early stage breast cancer. Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract S6-4.

6. Stopeck A, Martin M, Ritchie D, et al. Effect of denosumab versus zoledronic acid treatment in patients with breast cancer and bone metastases: results from the extended blinded treatment phase. Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract P6-14-01.

7. Rack B, Schindlbeck C, Andergassen U, et al. Prognostic relevance of circulating tumor cells in the peripheral blood of primary breast cancer patients. Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract S6-5.

8. Von Minckwitz G, Eidtmann H, Rezai M, et al. Neoadjuvant chemotherapy with or without bevacizumab: primary efficacy endpoint analysis of the GeparQunito Study (GBG 44). Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract S4-6.

9. FDA Begins Process to Remove Breast Cancer Indication from Avastin Label [news release]. US Food and Drug Administration website. Available at: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm237172.htm.

10. Amir E, Ocana A, Niraula S, Carlsson L, Seruga B. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients. Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract S2-7.

11. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. Journal of the American Medical Association. 2002;288(3):321-33.

12. Chlebowski RT, Schwartz AG, Wakelee H, Anderson GL. Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet. 2009;374:1243-51.

13. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. Journal of the American Medical Association. 2004;291(14):1701-12.

14. Ragaz J, Bajdik C, Wilson KS, et al. Dual estrogen effects on breast cancer: endogenous estrogen stimulates while exogenous estrogen protects. Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract P6-09-09.

15. Hornberger J, Chien R. Meta-analysis of the decision impact of the 21-gene breast cancer recurrence score in clinical practice. Paper presented at: 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2010; San Antonio, TX. Abstract P2-09-06.