If it is December, it must be time for the San Antonio Breast Cancer Symposium. Attendees at this meeting include scientists, clinicians, and advocates as well as representatives of companies that make breast cancer-related products. Researchers often save their biggest or most exciting results for this meeting. As a result, itâ€™s not uncommon for there to be what we call â€œpractice changingâ€ studies (research that will changes the way that doctors treat patients). So far nothing earthshaking has come out of this meeting, despite the media headlines you may have seen.
Thursday morningâ€™s session focused on the best way to use hormonal therapies to treat postmenopausal women with estrogen positive tumors. Currently, the options include either tamoxifen or an aromatase inhibitor. Although studies have found the aromatase inhibitors (AIs) to be a bit better than tamoxifen, there have been questions as to whether it was better to take an AI for five years or to start on tamoxifen for two to three years and then switch to an AI for the final two or three years. Others have questioned whether it would be better to start on an AI and then switch to tamoxifen.
This morning, we learned the results of several large studies exploring this question. The first study was a meta-analysis (a large analysis of a number of smaller studies. This study showed that woman who take AIs have a statistically significant 23% lower rate of recurrence (2.9% absolute decrease). However, there was no difference in survival. The researchers also looked at women who had taken tamoxifen and then switched to an AI after 2-3 years. In this group, there was a 29% relative decrease in recurrence (absolute risk 3.6%) and a statistically significant decrease in mortality without recurrence at 6 years of 0.7%.
A second study, which looked solely at the AI letrozole (brand name Femara), appeared to show that using letrozole was as good as switching. But the analysis is complicated by the fact that many women switched from tamoxifen after the initial AI data came out. So, this is far from the last word. The final study in this series looked at tamoxifen versus anastrozole (brand name Arimidex) in women who had invasive ductal cancer that was a grade 1 or 2 tumor or invasive lobular cancer. The study showed that the women who switched from tamoxifen to anastrozole after two to three years had an 18% decrease in recurrence. Furthermore, starting with tamoxifen and then switching to anastrozole significantly improved the relative risk of relapse-free survival by 27% and overall survival by 22%. Starting with anastrozole and then switching to tamoxifen resulted in a 21% decrease in relative risk and a 23% relative decrease in death. (Important note: These are relative risk reductions and not absolute risk reductions, which is why they look high.) So switching was better than just taking tamoxifen for five years, and the order did not seem to matter. The final presentation was on the TEAM study, which compared five years of exemestane (brand name Aromasin) with five years of tamoxifen. This study showed no difference between the two treatments. Bottom-line: It looks like a postmenopausal woman with estrogen positive cancer who has taken tamoxifen for two to three years should switch to an AI for the final two to three years of hormone treatment.
One of the most interesting observations was that nearly one-third of the women using tamoxifen and 20% of the women taking exemestane did not stay on their treatment for the full five years. Most likely this is due to the side effects of these drugs.
The afternoon session focused on surgical topics. One of the presentations was given by Dr. Todd Tuttle of the University of Minnesota, who discussed preventative mastectomy in women diagnosed with breast cancer. Many women think the risk of getting breast cancer in the other breast is really high. But he showed that it is actually a pretty low 0.7% per year and that was true for both ductal and lobular cancers. (Lobular cancers are usually thought to be more bilateral.) In addition, the risk is cut in half in women on hormonal therapy; reduced by 30% in women on chemotherapy; and reduced by 70% in premenopausal women who have their ovaries removed. So the actual risk of a second cancer in the other breast is closer to 0.2-.4%. Some factors of course increase this risk, like having a BRCA mutation or radiation exposure (for Hodgkinâ€™s disease).
Nonetheless, the number of contralateral prophylactic mastectomies (CPM) has gone up significantly. Rarely mentioned, though, is the risk of significant complications from this questionable procedure. Studies show that the overall complication rate is 16.3%, half of which are in the normal breast. Although CPM can reduce the risk of developing breast cancer on the other breast by 98%, it has no impact on a womanâ€™s overall survival. This is because the risk is low and most of the cancers that do develop can be detected and successfully treated. Also, what many women may not fully understand is that often the risk of the first cancer coming back is higher than the risk of getting a second cancer in the opposite breast. Dr. Tuttleâ€™s message was that we should be much more cautious about recommending or agreeing to complementary prophylactic mastectomy.
The most exciting talk of the day for me was Dr. Patricia Steegâ€™s discussion of metastatic disease. Head of Womenâ€™s Cancers at the NCIâ€™s Center for Cancer Research, Dr. Steegâ€™s research has helped us to better understand this complicated process. Her recent work has focused on brain metastases. Since our chemotherapies have gotten better, women are living longer, which has also increased the incidence of brain metastases. Dr. Steegâ€™s studies in animals have shown that some drugs get into the brain and others do not. They have also shown that women with HER-2 positive tumors seem to be more prone to brain metastases. Herceptin does not cross the blood-brain barrier. But the drug Lapatinib does, and it seems to have an effect on larger brain mets in animals. Another drug that has not been used in breast cancer, Vorinistat, also has been shown to reduce even minimal mets in the brain in animals, especially when combined with radiation. This work is very important to women with breast cancer and we hope studies on these drugs will soon begin in women. Anyone who is interested in this topic should check out the website www.brainmetsBC.org.
Stay tuned for notes from Day 2â€¦.