Musings: Post ASCO
Dr. Karen Gelmon, MD, FRCPC, Chair Breast Tumour Group, BC Cancer Agency

The American Society of Medicine's (ASCO) annual meeting usually brings new information of importance to the care and treatment of women with breast cancer. This year, it seemed although there were many good sessions, there were not any presentations that will significantly change how we think about the disease or the treatments which we deliver. However, there was reinforcement of a number of themes that have been previously identified.

Aromatase inhibitors such as letrozole (Femara), anastrozole (Arimidex) and exemestane (Aromasin) have been shown to have efficacy in recurrent or metastatic disease as both first and second line treatment and in certain adjuvant areas. Last fall, the results of MA17 were released. This study, led by the National Cancer Institute of Canada (NCIC-CTG), randomized postmenopausal women who had not recurred, to either letrozole (Femara) or a placebo after five years of tamoxifen. The published results showed a decrease in recurrence for those women treated with the aromatase inhibitor over the placebo suggesting a role for extended treatment. These results were updated in two important presentations. Dr. Paul Goss from Toronto, reported with further follow-up, letrozole improved survival for women who had involvement of axillary lymph nodes and showed no increased toxicity seen for those women treated with the extended treatment.

Dr. Tim Whelan, co-chair of the NCIC Breast Site, reported on the quality of life results from the MA17 study. Other than a mild decrease in the reported quality of life for women on the letrozole arm, mainly related to an increase in hot flushes and other vasomotor complaints, there was no major impact on quality of life for those women on the treatment compared with those not on the drug. What do these presentations tell us? They are further evidence of the impact and safety of aromatase inhibitors in the treatment of breast cancer. They do not clearly tell what is the best strategy of how to treat a postmenopausal women with a estrogen sensitive tumour, whether it is best to treat with Arimidex for five years, or tamoxifen for five years followed by Femara for five years, or tamoxifen for 3 years followed by Aromasin for 3 years? They do provide further evidence that there is a survival benefit potential and that they are safe and well tolerated. Women should have a discussion of these options with their oncologist.

As well, there was an update of a previously presented trial of postmenopausal women with estrogen receptor positive tumours with recurrent disease who were treated with exemestane or tamoxifen again showing a beneficial effect for the newer drug.

There were further presentations on the roles of bisphosphanates (prevents spread of cancer into bone) and on trastuzumab (Herceptin). In one presentation, using trastuzumab in the neoadjuvant setting (treatment given prior to surgery), the researchers bravely gave the drug concurrently with epirubicin (chemotherapy drug) despite concerns about the risk of heart failure. They showed very impressive results in terms of the number of women whose tumours had decreased prior to surgery and did not show significant early side effects on the heart. However, with fewer than two dozen women and without long term follow-up, it is not yet clear how safe this protocol will be and at this time it should be further studied.
Studies in bisphosphanates confirmed their safety and efficacy and we need to await the results of the recently closed study of clodronate (first generation bisphosphanate) in the adjuvant setting (B34 from the NSABP) to see if they should be more broadly instituted.

In one session focusing on women with genetic mutations which increase the risk of breast cancer, there was further emphasis placed on the role of MRI screening of the breast over mammography alone. Although MRI has been shown to have very good sensitivity, the specificity is poor, meaning it shows many changes in the breast that are not cancer. This increases the number of unnecessary biopsies and causes unwanted anxiety limiting its role for the general population. However, in women with an increased risk of breast cancer due to BRCA 1 or 2 mutations, who are often younger with dense breasts, MRI has consistently been shown helpful in conjunction with mammograms. In the studies reported, there was not a clear benefit in adding ultrasound examinations if MRI was being done, unless there was a specific mass that needed further assessment. The suggestion that oophorectomy (removal of the ovaries) decreases the rate of breast cancers in women with genetic mutations was discussed and it was suggested that for these women, if they were getting followed with regular mammograms, clinical examination and MRI, mastectomies could possibly be avoided.

In another study Dr. Eva Grunfeld showed women who had had breast cancer were more than adequately followed by their family physician and did not need to be seen in a cancer centre, assuming regular clinical examinations and mammograms were done and new complaints were promptly investigated.

What is really new? Many things, either not reported at this meeting or those which are in very early study. There are some exciting developments being made in how to diagnose breast cancers with new machines that may pick up the tension in the tissue and be more sensitive than anything we have now. There are new tests which may be able to soon pick up antibodies in the blood and allow earlier diagnosis. There are thousands of studies being done on the genes which make cancers grow and develop and with these studies, more understanding of how to develop drugs to target these tumours and stop their growth. But that is for the future. At this time, we can see small steps forward.

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