The 2009 San Antonio Breast Cancer Symposium

A December tradition for breast cancer researchers, this meeting highlights important advances in our understanding of an all-too-common disease.

By Kari Bohlke, ScD

The thirty-second CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) brought together more than 8,500 scientists and other professionals from more than 90 countries. The mission of the event is “to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for breast cancer patients.”

Bone Drug News

Bisphosphonates are a class of drugs used to prevent and treat osteoporosis and to reduce the risk of bone complications from bone metastases or multiple myeloma. Results presented at SABCS suggest that these drugs may also reduce the risk of breast cancer and may help prevent bone loss in breast cancer patients given certain types of hormonal therapy. Results were also presented at SABCS about a newer type of bone drug known as denosumab. Among breast cancer patients with bone metastases, denosumab may produce better results than a commonly used bisphosphonate.

Bisphosphonates May Reduce Breast Cancer Risk

Previous studies have suggested that intravenous bisphosphonates may inhibit breast cancer, but there has been less information about whether oral bisphosphonates affect breast cancer risk. To address this question, researchers evaluated information from the Women’s Health Initiative observational study.[1] The results indicated that postmenopausal women who used oral bisphosphonates were 32 percent less likely than other postmenopausal women to develop breast cancer. The most commonly used oral bisphosphonate was Fosamax® (alendronate). Similar findings were reported in a second study presented at SABCS, which reported a 29 percent reduction in breast cancer risk among postmenopausal women who used bisphosphonates for more than one year.[2]

Zometa Improves Bone Density Among Women Treated with Femara

Femara® (letrozole) is a type of hormonal therapy known as an aromatase inhibitor. Although aromatase inhibitors provide effective breast cancer therapy, they also contribute to bone loss. To determine whether treatment with a bisphosphonate can reduce this bone loss, researchers conducted a Phase III clinical trial known as Z-FAST (Zometa-Femara Adjuvant Synergy Trial).[3] The study enrolled postmenopausal women with Stage I–IIIA breast cancer. All the women received Femara as adjuvant (post-surgery) treatment. In addition, women were assigned to receive either immediate or delayed treatment with the bisphosphonate drug Zometa® (zoledronic acid). Immediate treatment with Zometa resulted in better bone mineral density than delayed treatment.

Denosumab Effective in Women with Bone Metastases

Denosumab is an investigational drug that targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Denosumab has shown promising results in the management of bone metastases, bone loss due to cancer treatment, and postmenopausal osteoporosis. The study presented at SABCS compared denosumab with Zometa among more than 2,000 breast cancer patients with bone metastases.[4] The results indicated that denosumab was more effective than Zometa at delaying or preventing bone complications such as fracture, radiation or surgery to the bone, and spinal cord compression.

HER2 News

Approximately 20 to 25 percent of breast cancers overexpress (make too much of) a protein known as HER2. Fortunately, the development of drugs that specifically target HER2-positive breast cancer has improved outcomes. These drugs include Herceptin® (trastuzumab) and Tykerb® (lapatinib).

Herceptin Given Concurrently with Chemotherapy May Provide Best Outcomes

The optimal timing of Herceptin was evaluated in a Phase III clinical trial known as NCCTG N9831.[5] The study enrolled women with Stage I–III HER2-positive breast cancer. All women received chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel, and some women also received Herceptin. Herceptin was given either at the same time as paclitaxel or later (after chemotherapy had been completed). The results of the study confirm that Herceptin improves outcomes among women with HER2-positive breast cancer; they also suggest that starting Herceptin at the same time as chemotherapy may produce better results than starting it after chemotherapy has been completed.

Combination of Herceptin with Non-anthracycline Chemotherapy Appears to Be Effective

The benefit of adding Herceptin to chemotherapy among women with early HER2-positive breast cancer was also evaluated in a clinical trial known as BCIRG 006.[6] Women were assigned to one of three treatment groups: (1) an anthracycline-based chemotherapy regimen, (2) an anthracycline-based chemotherapy regimen plus Herceptin, or (3) a non-anthracycline-based chemotherapy regimen plus Herceptin.

The results indicated that both of the Herceptin groups experienced a lower risk of cancer recurrence and better overall survival than the group that did not receive Herceptin. The results also indicated that survival and recurrence rates in the two Herceptin groups (anthracycline versus non-anthracycline) were not statistically significantly different from each other. Heart complications, however, were less common among women treated with non-anthracycline-based chemotherapy. This suggests that it may be possible to maintain effective cancer control with fewer heart complications by combining Herceptin with a non-anthracycline chemotherapy regimen. This point remains controversial, however.

Combination of Tykerb and Herceptin Benefits Patients Who Have Progressed on Herceptin

The combination of Tykerb and Herceptin was evaluated among women with metastatic HER2-positive breast cancer that had progressed during treatment with Herceptin.[7] Women were assigned to receive Tykerb alone or Tykerb in combination with Herceptin. Median overall survival was more than four months longer among women treated with Tykerb and Herceptin than among women treated with Tykerb alone.

Neratinib Shows Promise in Metastatic HER2-positive Breast Cancer

Neratinib is an investigational oral medication that targets HER2 as well as HER4 and the epidermal growth factor receptor (EGFR) pathway. In a Phase I–II clinical trial presented at SABCS, the combination of neratinib and paclitaxel chemotherapy produced promising response rates among women with metastatic HER2-positive breast cancer.[8] The combination of neratinib and paclitaxel is being evaluated further in a Phase III clinical trial.

Oncotype DX News

Oncotype DX® is a genomic test that has been shown to predict the likelihood of cancer recurrence in women with early-stage, estrogen receptor–positive breast cancer that is treated with hormonal therapy. Women with a low risk of recurrence may derive little benefit from chemotherapy. Oncotype DX evaluates the activity of 21 genes from a sample of the patient’s cancer to determine the patient’s recurrence score. The recurrence score ranges from 0 to 100, with a higher score indicating a greater risk of recurrence and benefit from chemotherapy. Oncotype DX has been added to U.S. medical guidelines for early-stage breast cancer.

Oncotype DX was initially validated among women with node-negative breast cancer, but the test also appears to provide important information about women with node-positive breast cancer. To further assess the test among women with node-positive, hormone receptor–positive breast cancer, researchers evaluated information from 367 patients.[9] Some patients received adjuvant therapy with tamoxifen alone, and some received tamoxifen plus anthracycline-based chemotherapy.

The addition of chemotherapy to tamoxifen significantly improved breast cancer survival among women with a high recurrence score but did not improve breast cancer survival among women with a low recurrence score. These results suggest that anthracycline-based chemotherapy may not benefit women with node-positive, hormone receptor–positive breast cancer and a low Oncotype DX recurrence score.

Another study presented at SABCS suggests that use of the Oncotype DX test among women with node-positive breast cancer can influence treatment decisions.[10] Most often the test was used to change the treatment plan from hormonal therapy plus chemotherapy to hormonal therapy alone.

Other Clinical Trial News

Avastin Improves Progression-free Survival in Advanced Breast Cancer, but Still No Evidence of Overall Survival Benefit

Avastin® (bevacizumab) is a targeted therapy that blocks a protein known as the vascular endothelial growth factor (VEGF). VEGF plays a role in the development of new blood vessels. The effectiveness of Avastin in the initial (first-line) treatment of locally advanced or metastatic breast cancer was evaluated in a study known as AVADO.[11] The results indicated that the addition of Avastin to chemotherapy improved response rates and delayed cancer progression. The addition of Avastin did not, however, improve overall survival. The role of Avastin in second-line treatment of metastatic HER2-negative breast cancer was evaluated in a study known as RIBBON-2.[12] Once again the addition of Avastin to chemotherapy delayed cancer progression. There was no significant difference in overall survival between study groups at the time of this interim analysis, but the study is ongoing. These studies indicate that the addition of Avastin to either first- or second-line chemotherapy delays the progression of advanced HER2-negative breast cancer. There is still no clear evidence, however, that Avastin improves overall survival.

Nexavar Evaluated in Locally Recurrent or Metastatic Breast Cancer

Nexavar® (sorafenib) is a targeted therapy that has been approved for use in selected patients with liver cancer or kidney cancer. To explore the potential role of Nexavar in the treatment of breast cancer, researchers conducted a Phase II clinical trial among 280 women with locally recurrent or metastatic HER2-negative breast cancer.[13] Women were assigned to be treated with paclitaxel chemotherapy alone or in combination with Nexavar. Progression-free survival was better among women treated with paclitaxel plus Nexavar than among women treated with paclitaxel alone (6.9 months versus 5.6 months). Women treated with the combination of drugs were also more likely to experience serious side effects of treatment, however.

Lifestyle News

Research into lifestyle factors that influence breast cancer risk or prognosis allows us to make more-informed decisions about how to manage our own health. Two factors that appear to affect not only the risk of developing of breast cancer but also the outcome of breast cancer are body weight and alcohol use.

Obesity Linked with Worse Outcomes

The impact of obesity on the prognosis of early breast cancer was evaluated in a study conducted in Denmark.[14] With information spanning 30 years, the researchers found that heavier women tended to have more-advanced breast cancer at the time of diagnosis than healthy-weight women. Heavier women also had an increased risk of distant metastasis and an increased risk of dying from breast cancer. These findings provide additional evidence regarding the importance of achieving and maintaining a healthy body weight.

Alcohol Consumption Increases Recurrence Risk

Previous studies have reported that alcohol consumption increases the risk of developing breast cancer, but there has been limited information about whether alcohol influences breast cancer prognosis and survival. To address this question, researchers evaluated information from the Life After Cancer Epidemiology (LACE) study.[15] The study enrolled 1,897 women who were diagnosed with early-stage, invasive breast cancer between 1997 and 2000. The researchers found that moderate-to-heavy alcohol consumption (at least three to four drinks per week) increased the risk of breast cancer recurrence by 30 percent. Women who were postmenopausal or overweight appeared to be most susceptible to the adverse effect of alcohol. In a prepared statement, the lead researcher suggested, “Women previously diagnosed with breast cancer should consider limiting their consumption of alcohol to less than three drinks per week, especially women who are postmenopausal and overweight or obese.”

References

[1]. Chlebowski R, Chen Z, Cauley JA, et al. Oral bisphosphonate and breast cancer: prospective results from the Women’s Health Initiative (WHI). Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 21.

[2]. Rennert G, Pinchev M, Rennert HS. Use of bisphosphonates and risk of postmenopausal breast cancer. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 27.

[3]. Brufsky A, Harker G, Beck JT, et al. The effect of zoledronic acid on aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: the Z-FAST study 5-year final follow-up. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 4083.

[4]. Stopeck A, de Boer R, Fujiwara Y, et al. A comparison of denosumab versus zoledronic acid on the incidence of skeletal-related events in breast cancer patients with bone metastases. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 22.

[5]. Perez E, Suman VJ, Davidson NE, et al. Results of chemotherapy alone, with sequential or concurrent addition of 52 weeks of trastuzumab in the NCCTG N9831 HER2-positive adjuvant breast cancer trial. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 80.

[6]. Slamon D, Eiermann W, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients: BCIRG 006 study. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 62.

[7]. Blackwell KL, Burstein HJ, Sledge GW, et al. Updated survival analysis of a randomized study of lapatinib alone or in combination with trastuzumab in women with HER2-positive metastatic breast cancer progressing on trastuzumab therapy. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 61.

[8]. Chow L, Gupta S, Hershman DL, et al. Safety and efficacy of neratinib (HKI-272) in combination with paclitaxel in ErbB2+ metastatic breast cancer. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 5081.

[9]. Albain KS, Barlow WE, Shak S, et al. Prediction of 10-year chemotherapy benefit and breast cancer-specific survival by the 21-gene recurrence score (RS) assay in node-positive, ER-positive breast cancer: an update of SWOG-8814 (INT0100). Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 112.

[10]. Oratz R, Chao C, Skrzypczak S, et al. Effect of 21-gene recurrence score results on treatment recommendations in patients with lymph node-positive, estrogen receptor-positive breast cancer. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 2031.

[11]. Miles DW, Chan A, Romieu G, et al. Final overall survival (OS) results from the randomised, double-blind, placebo-controlled, Phase III AVADO study of bevacizumab (BV) plus docetaxel (D) compared with placebo (PL) plus D for the first-line treatment of locally recurrent (LR) or metastatic breast cancer (mBC). Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 41.

[12]. Brufsky A, Bondarenko IN, Smirnov V, et al. RIBBON-2: a randomized, double-blind, placebo-controlled, Phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of HER2-negative metastatic breast cancer. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 42.

[13]. Gradishar W, Kaklamani V, Prasad Sahoo T, et al. A double-blind, randomized, placebo-controlled, Phase 2b study evaluating the efficacy and safety of sorafenib in combination with paclitaxel as a first-line therapy in patients with locally recurrent or metastatic breast cancer. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 44.

[14]. Ewertz M, Jensen MB, Gunnarsdottir K, Cold S. Effect of obesity on prognosis after early breast cancer. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 18.

[15]. Kwan ML, Kushi LH, Weltzien E, Castillo A, Caan BJ. Alcohol and breast cancer survival in a prospective cohort study. Paper presented at: 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 17.