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Meeting features latest research findings

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  2. Meeting features latest research findings

New discoveries in prevention, laboratory, and translational and clinical breast cancer research were announced at this year's 33rd Annual San Antonio Breast Cancer Symposium, sponsored by the Cancer Therapy and Research Center at the University of Texas Health Science Center in San Antonio and the American Association for Cancer Research.

The December 2010 symposium drew nearly 9000 participants from more than 90 countries and included findings in the following areas:

Obesity

Obese women with operable breast cancer who were treated with adjuvant chemotherapy had worse overall and disease-free survival and, for the first time, the finding was observed only in patients with estrogen receptor (ER)- positive/human epidermal growth factor receptor 2 (HER2)-negative disease. Researchers from the Albert Einstein College of Medicine in New York City conducted a retrospective study to evaluate the effects of obesity in 3 Eastern Cooperative Oncology Group trials. They plan additional studies to evaluate the relation between obesity and tumor gene expression and to evaluate other factors that may be associated with disease recurrence.

Screening

Most women do not undergo recommended mammograms. An analysis of women aged 40 to 85 years showed that only 50% had a mammogram in any given year, and only 60% underwent 2 or more mammograms in 4 years. The study, led by Milayna Subar, MD, of Medco Health Solutions, Inc, in Franklin Lakes, New Jersey, reviewed medical claims made between January 2006 and December 2009 from a database of more than 12 million individuals who have private insurance or Medicare coverage. Researchers did not examine why women were not getting screened, but theories include discomfort from the test, a lack of screening centers, non compliance, or denial.

Heart Disease

Aromatase inhibitors, which block the production of estrogen, cause a significant increase in side effects such as heart attack, angina, and heart failure in postmenopausal women with breast cancer, according to research from the Princess Margaret Hospital in Toronto, Ontario, Canada. Researchers conducted a meta-analysis to determine whether the increased risk of heart disease occurs with any aromatase inhibitor. They examined data from 7 large clinical trials comparing tamoxifen with aromatase inhibitors in postmenopausal women with early stage breast cancer and found that any duration of use of the latter was associated with a 20% higher probability of developing cardiovascular disease; however, the use of aromatase inhibitors also was associated with a reduced risk of venous thrombosis and endometrial cancer.

Hormone Replacement Therapy

Hormone replacement therapy (HRT) using estrogen alone (exogenous estrogen) provides a protective effect and can reduce breast cancer risk, according to researchers from the School of Public Health at the University of British Columbia in Vancouver, Canada.

Endogenous estrogen has a well-known carcinogenic effect, but these results should encourage new research into exogenous estrogen as a protective agent against breast cancer, the researchers note. The researchers reviewed and analyzed data from the Women's Health Initiative HRT trials and found that subsets of women without a strong history of breast cancer who received estrogen alone had a significantly reduced breast cancer incidence. In addition,75% of women without benign disease prior to enrollment were found to have a reduced breast cancer risk.

Investigators note that further research is needed to determine the optimum treatment regimen, refine the selection of ideal candidates for estrogen therapy, and understand the mechanisms that help prevent cancer.

Risk of Disease Recurrence

Circulating tumor cells (CTCs) predicted disease recurrence and death in patients with early stage breast cancer. According to phase 3 results of the Simultaneous Study of Gemcitabine-Docetaxel Combination adjuvant treatment, as well as Extended Bisphosphonate and Surveillance (SUCCESS) trial, the presence of 1 to 4 CTCs in the blood of patients with early stage cancer almost doubled their risk for cancer recurrence and death, whereas 5 or more CTCs increased the risk of recurrence by 400% and that of death by 300%.These cells were found in patients after surgery but before chemotherapy.

The CTCs in the study likely indicate that a tumor is shedding breast cancer cells, says lead researcher Brigitte Rack,MD, head of the department of gynecological oncology at the University of Munich in Germany. The survival of these CTCs after chemotherapy suggests that they are cancer stem cells, she adds.

The SUCCESS trial is testing the effectiveness of 2 different chemotherapy regimens and extended adjuvant bisphosphonate treatment in patients with early breast cancer. Results are expected next year. Being CTC positive was found to be a significant independent predictor for disease free survival and overall survival. Patients with 1 to 4 CTCs had an 88% increased risk of early breast cancer recurrence and a 91% increased risk of death from breast cancer.

Results indicate that patients who appear to be at high risk due to CTCs may benefit from additional treatment options, whereas those who do not have CTCs may be able to avoid certain treatments, Dr. Rack notes. She adds that prospectively randomized trials are needed to demonstrate an improvement in survival based on CTC diagnostics. Such trials are ongoing or about to start in Europe and the United States.

Prognosis Predictors

A high level of CTCs is an independent prognostic marker for metastatic breast cancer and an early marker of poor outcomes, according to a study from researchers at the Institut Curie and Université Paris Descartes, both in Paris, France. Previous research has not indicated that the routine use of CTC tests can improve patient outcomes and therefore such testing is not a recommended practice, says Jean-Yves Pierga, MD, PhD, professor of medical oncology at the Institut Curie.

Researchers tested CTC levels as an outcome predictor compared with serum tumor markers in patients with metastatic breast cancer who were treated with first-line chemotherapy. Tumor markers only indirectly reflect the presence of cancer, and some breast cancers can metastasize without any increase in tumor serum markers, Dr. Pierga says.

In the study of 267 patients with metastatic breast cancer, high CTC levels were found to be predictive of poor progression-free survival and overall survival, independent of serum tumor markers. They also were independent of tumor biology, such as HER2 status or grade of cancer.

Health Insurance

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Results indicate that patients who appear at high risk due to CTCs may benefit from additional treatment options while those who don't have CTCs may be able to avoid certain treatments.

—Brigitte Rack, MD

Researchers at Columbia University in New York City reported that higher prescription copays, particularly among older women, led to both the early discontinuation and incomplete use of adjuvant aromatase inhibitors for women with early stage, hormone-sensitive breast cancer.

Dawn Hershman, MD, MS, associate professor of medicine and epidemiology at Columbia University, and colleagues gathered anonymous patient information from women aged 50 years and older who were prescribed aromatase inhibitors for early breast cancer. They focused on those who discontinued use of the medication completely or had no subsequent refills and those who did not refill their prescription on time or did not take the medication at least 80% of the time.

Results showed that 21.1% of 8110 women between ages 50 and 65 years stopped taking the medication and, of those who continued with their regimen, 10.3% did not take the medication as directed over the 2-year period. Of the 14,050 women aged 65 years or older, nearly 25% stopped taking the medication, whereas 8.9% who continued were nonadherent.

In the group of patients aged 65 years and older, women were more likely to discontinue their medication if their copays were above $30. It was not until the copayment reached $90 or more that the patients ages 50 to 65 years were more likely to discontinue use or not take it as prescribed. Furthermore, women whose prescriptions came from a primary care physician or who were prescribed many other medications also were more likely to stop the medications or not take them as prescribed.

Dr. Hershman concludes that future policy efforts should focus on reducing financial constraints to ensure the effective use of these medications.