After Dr. Monica Morrow finished her important discussion on breast MRI, we moved on to another topic of interest: The ability of the OncotypeDX test, which is used to assess recurrence risk in women with early stage disease, works as well in women whose tumors have already spread to their lymph nodes.
Over the past decade, we have learned that not all breast cancers behave in the same way and that different types of cancers respond to different treatments. As a result, scientists have been studying ways to try to determine which tumors are which. The Oncotype DX test is one attempt to figure this out. The test uses a panel of biomarkers to assess whether a woman is at high, medium, or low risk for recurrence. Previous studies showed that the test worked well in women who had ER-positive tumors that were node-negative. They also showed that the women with the low score do well with tamoxifen and get little benefit from chemotherapy.
Last year, the researchers reported that the test worked well in node-positive women, showing that the biology of the tumor is more important that its stage. Then, they went a step further, looking at women who are estrogen positive and node positive and were treated with either tamoxifen or the aromatase inhibitor anastrozole (brand name Arimidex.) This was the largest study of this test and it came out with flying colors, showing again that even in women with positive nodes the test can distinguish those who are high risk from those who are low risk as well as identify who needs hormonal treatments and who needs chemotherapy.
One way to think about this is to make an analogy with antibiotics. If you have an infection caused by a certain bacteria, it is important to take the antibiotic that will treat that specific type of bacteria. If you have a really bad infection, you donâ€™t switch to a stronger drug. Instead, you switch to the antibiotic that will treat that specific type of bacteria. The Oncotype DX is a test that can help us figure out which treatment is likely to be the best for your ER-positive tumor, regardless of whether your nodes are positive.
Other tests are being explored for ER-negative breast cancer and, in fact, some of yesterday’s data suggested there may soon be a way to figure out which HER2/neu drug (Tykerb or Herceptin) would be a better match for your tumor. The era of personalized medicine is getting closer!
The afternoon was the best part of the entire meeting. First, we heard a very interesting mini-symposium on the microenvironment of the tumor. For many years, we have focused our research on the cancer cell and its molecular biology. This work has allowed us to learn more about tumors, but it has only had a small impact on the way we treat breast cancer. Finally we are recognizing that the cancer cell does not live in isolation but in a microenvironment of stroma (think of blue cheese: the blue represents the ducts and epithelial cells and the white the stroma in which they are suspended).
Some of the most interesting recent research studies have shown us that that the stroma affects how the epithelial cells behave. We have also learned that estrogen significantly affects the stroma, making it more supportive of invasion. These studies are very interesting as they are helping us to figure out which stromal cells do what and when to achieve this effect. But even more importantly, it is shedding light on how hormones, breast density, and breast cancer interact. For example, researchers from the Mayo Clinic presented two posters that showed that breast density represents the stromal cells and relates to the level of aromatase that is present. (Aromatase is the enzyme that converts precusors into estrogen in postmenopausal women).
In the second presentation of the afternoon, we learned that high-risk women on tamoxifen who have their breast density decrease by 10% are at lower risk of developing ER-positive breast cancer. This is exciting news on several fronts. It provides a good way for us determine whether tamoxifen is helping a high-risk women. It also gives us a clue as to how HRT causes breast cancer, since we know that HRT increases breast density and increases breast cancer.
I was happy to see investigators present follow up data from the Womenâ€™s Health Initiative (WHI) study on HRT. Last year at this meeting, the WHI data released showed that there was a 15% decrease in the incidence of breast cancer as women stopped taking the drugs abruptly. The proponents of HRT argued that the effect would not last, and that it the decrease in breast cancer was probably related to a decrease in mammograms that year. Todayâ€™s presentation squelched that theory, as it showed that the decrease in breast cancer risk persisted through 2005. Furthermore, there was no evidence of a decrease in the use of mammography. Finally, as I reported earlier, the California Teacherâ€™s Study showed us that women who get breast cancer on HRT have â€œgoodâ€ breast cancers. While this might be a source of relief for women in that situation, it certainly does not mean that it is okay. That â€œgoodâ€ breast cancer still has to undergo surgery, radiation, hormone therapy, and maybe chemotherapy.This led me to think about how we can put all of these pieces of information together. The effect of estrogen on the stroma gives us a potential mechanism for understanding effects of both HRT and tamoxifen. It also helps us to understand why their effect is so rapid. They are not causing mutations to develop in the epithelial cells that could lead to cancer, as this would take a long time. Rather, they are changing the local environment surrounding the epithelial cells, which results in much more rapid changes. This suggests that any woman who is put on HRT and who sees an increase in her breast density should consider stopping whereas a woman whose breast density remains stable may be okay. I think this is a hypothesis worth testing.
The final talk was sobering. In most of the world, a drug called tibilone is used to treat hot flashes. Studies had found that it appeared to be safe and that in addition to reducing hot flashes it increased bone density, decreased fractures, and decreased breast cancer. This made it look like it could be a good alternative to HRT, since it reduced hot flashes, was good for the bones, but didnâ€™t increase breast cancer risk. So, researchers initiated a study in which women with breast cancer who had hot flashes caused by tamoxifen or an aromatase inhibitor were given tibilone to see if it would help them, too. Unfortunately and surprisingly, tibilone was found to increase a womanâ€™s risk of having a breast cancer recurrence. This was especially true for the women on aromatase inhibitors as their risk of recurrence more than doubled. This is why we have to do studies and not just assume that everything will be okay.