Classification of Adult Sarcomas

Scientists have demonstrated that genetic "fingerprinting" can help classify subtypes of soft-tissue sarcomas that otherwise look virtually identical. Soft-tissue sarcomas begin in tissues such as fat, muscles, nerves, tendons, and blood vessels. There are more than 50 known subtypes of soft-tissue sarcomas.

For decades, many pathologists have lumped difficult-to-diagnose sarcomas into a "catch-all" category called malignant fibrous histiocytomas (MFH). With current treatments, about 50% of patients with MFH sarcoma survive long-term.

Doctors have long debated whether MFH is one distinct subtype of sarcoma. In this study, researchers used a gene technology called oligonucleotide array analysis to analyze the pattern of activity of 12,500 genes from 52 subtypes of adult soft-tissue sarcoma on a single slide, or "chip." This provides a genetic fingerprint unique to each subtype of sarcoma.

The analysis could easily distinguish between sarcomas with specific genetic alterations. But the technology also differentiated between certain MFH sarcomas and found that some of them formed a distinct subtype. Genes characteristic of each sarcoma subtype were identified. (Abstract # 1611)

What does this mean for patients?

This discovery opens the door to better diagnosis of sarcoma, and may lead to new, more targeted treatments that attack sarcomas based on their genetic differences.

"Genetic fingerprinting of adult sarcomas will likely be useful when pathologists disagree about a diagnosis or when the appearance of tumor cells does not conclusively link them to a particular subtype," said lead investigator Robert Maki, MD, a medical oncologist at Memorial Sloan-Kettering Cancer Center.

Genetic fingerprinting technology may also help scientists evaluate how genes in cancer cells are turned on or off in response to therapy. That will help to determine if a particular sarcoma subtype will eventually become resistant to a given treatment, said Dr. Maki.
Breast Cancer: ASCO Recommendations on Aromatase Inhibitors

Aromatase inhibitors are a class of hormone treatments designed to reduce the amount of estrogen in a womanÆs body and slow or stop the growth of breast cancers that are estrogen "receptor-positive" (tumors that grow faster on estrogen). Aromatase inhibitors are newer treatments, and show some promise in preventing recurrence in women with early stage breast cancer.

Tamoxifen is another hormone treatment for breast cancer. It blocks the effects of estrogen on tumor growth, and has proven to prevent recurrence in women with early stage breast cancer. It has been studied for 30 years and the benefits and side effects are well known.

To see if aromatase inhibitors are more effective than tamoxifen, researchers have started a five-year clinical trial called the ATAC trial (Arimidex (anastrozole), Tamoxifen Alone or in Combination). In 2001, researchers released some early results of the trial, which show that anastrozole is effective in reducing risk for recurrence, maybe more than tamoxifen.

After the results were released, ASCO formed a panel of breast cancer experts to assess aromatase inhibitors. This is the first independent assessment of aromatase inhibitors for the prevention of breast cancer recurrence following surgery. The panel finds that the early results are promising but does not support routine use outside of clinical trials.

ASCO examined the ATAC trial, published medical literature, and unpublished data from drug companies on planned and ongoing studies. Their report is one of ASCOÆs Technology Assessments, designed to recommend if new procedures, tests, or devices are appropriate for broad use.

ATAC Trial Findings

The ATAC study is designed to compare anastrozole and tamoxifen for five years. It includes over 9,000 women with early stage breast cancer. All women in the study had received primary surgery and were candidates to receive adjuvant (added) hormonal therapy.

After a median of 33 months, 317 of the 3,125 women taking anastrozole had a relapse of breast cancer or died, compared to 379 of the 3,116 women on tamoxifen. This is a 17% reduction in the risk of recurrence with anastrozole compared to tamoxifen.

The impact of anastrozole on patient survival has not yet been formally studied.

Findings of ASCOÆs Expert Panel

The reduction in breast cancer recurrence seen in the ATAC trial is promising. However, the panel found that it is premature to recommend anastrozole for routine use. Because tamoxifen provides its greatest benefit when taken for five years, the two drugs cannot be properly compared until anastrozole has been tested for five years also.

While there were few serious side effects in the ATAC trial for both anastrozole and tamoxifen, the long-term side effects of anastrozole are still unknown. Since there is extensive, long-term data on tamoxifen and a clearer understanding of its risks, the panel recommends that tamoxifen remain the standard of care.

The expert panel found no evidence to suggest that women who have started a standard course of tamoxifen should switch to anastrozole or other aromatase inhibitors.

For women who cannot take tamoxifen for specific reasons or severe side effects, anastrozole may be an option. Healthcare providers and women should make decisions with careful consideration of all the available data.

ASCO Assessment of Tamoxifen and Raloxifene

ASCO has also updated its recommendations on the use of hormonal therapies for reducing breast cancer risk in pre-menopausal women at elevated risk. The results of a new technology assessment recommend that women age 35 and over with a five-year projected breast cancer risk of greater than 1.66 should be considered candidates for tamoxifen. The updated assessment confirms ASCOÆs recommendations from 1999.

The assessment also found there is not enough evidence to suggest that raloxifene or aromatase inhibitors be used for breast cancer risk reduction.

To see the original assessment, or ASCOÆs other guidelines, visit www.asco.org or call 703-299-0150.

What does this mean for patients?

These findings represent no change in the current recommendations for women with early breast cancer.

"Patients and physicians can rest assured that tamoxifen remains the best option for use outside of clinical trials, and that it reduces the risk of recurrence and improves overall survival with manageable side effects for most women," said Eric Winer, MD, Director of the Breast Oncology Center at the Dana-Farber Cancer Institute and chair of the panel. "While recent findings on the use of aromatase inhibitors for the prevention of breast cancer recurrence are encouraging, data on long-term use of the drugs are needed before a change in the standard of care is justified."

Women interested in a clinical trial of anastrozole should talk with their doctor.