Metastases from Breast Cancer May Differ from Primary Tumor

It appears that in metastatic breast cancer, the biologic characteristics of liver metastases sometimes differ from those of the primary tumor. This finding may affect treatment choices for metastases. Results of this retrospective study were presented at the 2010 annual meeting of the American Society of Clinical Oncology.

Three key biologic markers are used to determine treatment for breast cancer. These are estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. These markers are expressed as positive or negative and affect the way the cancer grows. Because certain drugs are designed to stop the growth of cancer according to these markers, ER, PR, and HER2 status guide treatment choices.

The treatment of metastatic cancer (cancer that has spread to other parts of the body), is often based on the biologic markers of the primary tumor. Metastatic cancer is not always biopsied to determine its own biologic markers. If, however, metastatic cancer, such as liver metastases, has markers that differ from those of the primary tumor, the original treatment plan may not be as effective.

To evaluate the extent to which characteristics between primary breast tumors and metastases to the liver may differ, researchers in Italy compared tumor biopsies from 255 women.

Changes in ER status (from ER-negative to ER-positive and vice versa) were observed in 14.5% of liver metastases.Changes in PR status were observed in 48.6%.Changes in HER2 status were observed in 13.9%.Changes in tumor characteristics from primary to metastatic tumors resulted in changes in treatment plan for 12.1% of women.

The researchers concluded that because biologic markers of liver metastases may differ from those of primary breast tumors, biopsy of liver metastases should be considered. Accurate classification of secondary tumors by these markers may influence treatment choices.

Reference: Locatelli MA, Curigliano G, Fumagalli L, et al. Should liver metastases of breast cancer be biopsied to improve treatment choice? Presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract CRA 1004.

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Xgeva Approved for Patients with Bone Metastases

Xgeva? (denosumab) has been approved by the US Food and Drug Administration (FDA) for the prevention of bone complications such as fracture in patients with bone metastases from solid (not blood-related) cancers. It is not approved for patients with multiple myeloma or other cancers of the blood.

Metastatic cancer refers to cancer that has spread to distant sites in the body. Several types of 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.

Denosumab is a drug that targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Denosumab was initially approved under the trade name ProliaR for the treatment of osteoporosis in postmenopausal women; it is now also approved under the trade name Xgeva for patients with bone metastases. Xgeva is administered using a higher dose and with more frequent dosing than Prolia.

The safety and efficacy of Xgeva were established in three clinical trials that compared Xgeva to the bisphosphonate drug ZometaR (zoledronic acid). One of the studies enrolled patients with breast cancer, one enrolled patients with prostate cancer, and the third enrolled patients with a variety of cancer types.

The studies assessed the frequency and timing of bone complications (“skeletal related events”). The bone complications that were evaluated were fracture, radiation to the bone, surgery to the bone, and spinal cord compression. In the studies of breast and prostate cancer patients, Xgeva delayed bone complications to a greater extent than Zometa. In the study of patients with other cancer types, Xgeva and Zometa produced similar results.

The approval of Xgeva expands the treatment options available to patients with bone metastases.

Reference:? US Food and Drug Administration news release. FDA approves Xgeva to help prevent cancer-related bone injury. November 19, 2010.

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Cabozantinib Shows Promise against Bone Metastases

The investigational drug cabozantinib is showing promise against several types of advanced cancer, and may also reduce or eliminate bone metastases (cancer that has spread to the bone) in some patients. These results will be presented at the 2011 annual meeting of the American Society of Clinical Oncology.?

Metastatic cancer refers to cancer that has spread to distant sites in the body. Several types of cancer—including cancers of the prostate, lung, and breast—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. ?

Cabozantinib is an investigational drug that targets two proteins—MET and VEGFR2—that play a role in the development and progression of many types of cancer. ?

To evaluate cabozantinib in the treatment of advanced cancer, researchers conducted a Phase II clinical trial among 398 patients. The nine types of cancer included in the study were breast, stomach/gastroesophageal junction, non-small cell lung, ovarian, pancreatic, hormone-refractory prostate, small cell lung, liver, and melanoma. At the start of the study, 39% of the patients had bone metastases.?

Patients were initially treated with 12 weeks of cabozantinib. After 12 weeks, patients who had a partial response to treatment (a reduction in detectable cancer) remained on cabozantinib, patients with stable disease (no significant change in the cancer) were randomly assigned to either continue with cabozantinib or to take a placebo, and patients with progressive (worsening) cancer were withdrawn from the study.?

By week 12, 9% of patients responded to treatment. ?For some types of cancer, cabozantinib produced high disease control rates (defined as either a reduction in cancer or stable disease). The disease control rates were 76% for liver cancer, 71% for prostate cancer, and 58% for ovarian cancer.?Among the 68 patients with bone metastases, 59 had partial or complete disappearance of the cancer on bone scans, often accompanied by significant pain relief. A majority of these patients had hormone-refractory prostate cancer, but patients with breast cancer and melanoma also experience a disappearance of bone metastases. The researchers had not expected this result.?The most common side effects were fatigue and hand-foot syndrome (pain, swelling, numbness, tingling, or redness of the hands or feet).?

In a prepared statement, the lead author of the study noted “Cabozantinib appears to have significant effects on several treatment-resistant tumors, as well as impressive effects on bone metastases. In addition, these effects are associated with rapid improvement in pain, a reduction in opiate narcotic requirements and improvement in anemia. The implications of these results are very exciting—it is unusual to find a targeted therapy, absent of a molecular mutation in tumors, that works in bony disease and has this activity.”?

Research on cabozantinib continues. ?

Reference: Gordon MS, Vogelzang NJ, Schoffski P et al. Cabozantinib (XL184) has activity in both soft tissue and bone: Results of a phase II randomized discontinuation trial (RDT) in patients (pts) w/ advanced solid tumors. Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 3010.?

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Hidden Lymph Node Metastases Have Small Effect on Breast Cancer Outcomes

Among women with early breast cancer and a sentinel lymph node that appears to be cancer-free on routine evaluation, more extensive lymph node evaluation identifies small areas of cancer in approximately 16% of women. These small, hidden areas of cancer appear to have only a small effect on cancer outcomes, suggesting that current approaches to lymph node evaluation are adequate. These results were published in the New England Journal of Medicine.

For women with early breast cancer, determining whether the cancer has spread to the axillary (under the arm) lymph nodes is an important part of cancer staging. Evaluation of the axillary nodes may involve either an axillary lymph node dissection (ALND), in which many lymph nodes are surgically removed and evaluated, or a less extensive procedure known as a sentinel lymph node biopsy.

Sometimes, very small areas of cancer may be missed on routine lymph node evaluation. These areas of cancer are referred to as “occult” (hidden) metastases. Some previous studies have found that breast cancer patients with occult lymph node metastases have worse outcomes than patients with lymph nodes that are truly cancer-free.

To further evaluate the importance of occult lymph node metastases, researchers evaluated information from the NSABP-B32 study. The primary objective of the study was to evaluate the safety and effectiveness of sentinel lymph node biopsy, but researchers have also been able to explore other questions, including the impact of occult metastases.

The current analysis focused on 3,887 women with sentinel lymph nodes that were negative (cancer-free) on routine evaluation. These lymph nodes underwent further evaluation in an effort to detect occult metastases.

Occult metastases were detected in 16% of patients.The presence of occult metastases was linked with a higher rate of recurrence and worse survival, but these effects were small. Five-year overall survival, for example, was 94.6% among women with occult metastases and 95.8% among women without occult metastases.

The researchers conclude that although occult metastases appear to influence breast cancer outcomes, the magnitude of the effect is very small. Efforts to detect occult metastases appear unlikely to provide much benefit. The researchers note that continued follow-up is warranted, and it remains possible that these results will change as more information becomes available. ?

Reference: Weaver DL, Ashikaga T, Krag KN et al. Effect of occult metastases on survival in node-negative breast cancer. New England Journal of Medicine. Early online publication January 19, 2011.

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Herceptin and Chemotherapy Benefit Breast Cancer Patients with Brain Metastases

Among women with HER2-positive breast cancer that has spread to the brain, treatment with HerceptinR (trastuzumab) and/or chemotherapy can prolong survival. These results were published in Clinical Cancer Research.???

Although important advances have been made in breast cancer treatment, the treatment of metastatic breast cancer (breast cancer that has spread to other parts of the body) remains challenging. The brain is one area to which breast cancer may spread, and researchers continue to explore how best to manage patients with brain metastases.?????

To assess the frequency and outcome of brain metastases in women with metastatic HER2-positive breast cancer, researchers conducted a study among 1,023 newly diagnosed patients. HER2-positive breast cancer refers to cancer that overexpresses (makes too much of) the HER2 protein. Treatment of HER2-positive breast cancer often includes a HER2-targeted therapy such as Herceptin.???

Brain metastases were more common in younger women, those with hormone receptor-negative breast cancer, and those with a greater amount of cancer.?Among women who were free of brain metastases at the time of their initial diagnosis but later developed brain metastases, brain metastases were diagnosed a median of 13 months after initial diagnosis.?After the diagnosis of brain metastases, treatment with Herceptin and chemotherapy each significantly improved overall survival.??

These results suggest that even after HER2-positive breast cancer spreads to the brain, standard breast cancer treatments can prolong survival.?

Reference: Brufsky AM, Mayer M, Rugo HS et al. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clinical Cancer Research. 2011; 17: 4834–43.?

Posted July 20, 2011

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