In the breast cancer world, the annual San Antonio Breast Cancer Symposium is the big event. The 2014 meeting, held from December 9 through December 13, brought together about 7,500 doctors, researchers, and advocates from more than 90 countries. Seeking and expecting important news, reporters from throughout the world attend the Symposium as well. A quick Google search shows 6,650 news stories coming out of this year’s symposium. But what’s “news” is not always the real story. Here’s the news that I think matters: TUMOR SUBTYPES We’ve known for some time that breast cancer is not just one disease. Now, more research is being done to divide up the categories we’ve had into even smaller subgroups. This is being done, in part, to determine if there are certain subgroups of patients who have tumors that will benefit from a treatment that, at first glance, doesn’t appear to be effective when all of the groups are lumped together. It is also being done to identify mutations that identify these subgroups. What has this taught us?We’ve learned thattumors areheterogeneous. This means that not every cancer cell in the tumor necessarily carries the same mutations, which means a biopsy may not give you the full picture of the tumor. It also means that when tumors metastasize, cancer cells in different parts of the body might have different mutations. This could be related to the microenvironment of the area in which the cancer cells have landed. It could also be related to previously used treatments. We’ve known that tumors that are HER2+ can, after they have been treated with Herceptin, become HER2-. This is “bad” news because it means that we need to reassess how we think about how we classify tumors. At the same time, it’s good that we know it because it means we can think more critically about how often metastases should be tested, where these biopsies should be done, and when treatments should change. We are learning that certain treatments might work only in the right subgroup. One example of this is the research presented at San Antonio about bevacizumab (Avastin). Researchers took another look at data on women with triple negative breast cancer enrolled in the CALGB 40603 trial by dividing them into two subtypes: basal-like and non-basal-like. In this study, patients were given Avastin or carboplatin and standard paclitaxel (Taxol) prior to surgery (this is called neoadjuvant treatment). Giving treatment before surgery allows researchers to study how the tumor has responded to the therapy. The subgroup analysis found that when Avastin was given along with Taxol, there was a statistically significant improved rate of pathological complete response (PCR)—meaning the tumor is no longer visible at the time of surgery—in patients with the basal-like tumors, but not in those with non-basal-like tumors. Looking even more closely at the tumors, the researchers found that Avastin also improved PCR in patients whose tumors had high proliferation (meaning they were growing quickly), had low estrogen expression, or had a TP53 mutation—all of which suggest a tumor with a more aggressive biology. Why is this important? When we first saw the data from this study, we didn’t think Avastin should be used to treat triple-negative tumors. Now, it makes us think that there may be a subgroup of patients with triple-negative tumors who will benefit when Avastin is added to chemotherapy. ESTROGEN IS KEYTamoxifen for breast cancer prevention puts the focus back on estrogen.  The IBIS Breast Cancer Prevention Study was designed to see if 5 years of tamoxifen reduced the risk of breast cancer in high-risk women. In this study, 7,154 women ages 35 to 70 were randomly assigned to take tamoxifen or a placebo for 5 years. In both groups, women were allowed to take hormone replacement therapy (HRT). The researchers have now followed these women for 16 years, and the latest data show there have been 251 cancers (7.8%) in women who were in the tamoxifen group and 351 cancers (12.3%) among those in the placebo group. Looking more closely, the study showed that the women who took HRT did not benefit from tamoxifen, illustrating again the link between HRT and breast cancer risk. Another concern about tamoxifen, especially when it is used for breast cancer prevention, is that it increases the risk of uterine cancer. In the IBIS study, there have now been 29 women in the tamoxifen group and 20 in the placebo group who developed uterine cancer. The updated data presented at San Antonio also showed that tamoxifen is decreasing ER+ tumors and ductal carcinoma in situ (DCIS) but not ER-negative cancers. It also showed that there were slightly more breast cancer deaths among the women who took tamoxifen (31 compared to 26 in the placebo group). One hypothesis that the researchers proposed is that tamoxifen makes some tumors that would have emerged as ER+ mutate into ER- tumors. However, it will take another 10 years to have enough data to know. So, if you are considering taking tamoxifen for breast cancer prevention, the facts you will want to consider are: 1) that we need to treat 22 women with tamoxifen for 5 years to prevent one breast cancer; and 2) that the prevention benefit continues long after you stop taking the drug. Ovarian suppression can benefit premenopausal breast cancer patients who do not go into menopause after chemotherapy. This year, we heard long-awaited results from the SOFT study, one of three trials initiated to identify the best way to treat premenopausal women with hormone-sensitive tumors. SOFT enrolled 3,000 premenopausal women with ER+ tumors who were going to receive hormone therapy. They were randomly assigned to receive tamoxifen alone; ovarian suppression (temporary with injections, or permanently with surgery or radiation) and tamoxifen; or ovarian suppression and exemestane (Aromasin), an aromatase inhibitor, which can only be given to women who are postmenopausal. After following the women for 5.6 years, the researchers found that young women who had remained premenopausal after chemotherapy benefitted from ovarian suppression. The group who received ovarian suppression in addition to tamoxifen had fewer recurrences than the group that received only tamoxifen. Using the aromatase inhibitor Aromasin following ovarian suppression offered slightly more benefit. To date, ovarian suppression has been more commonly used in Europe than in the U.S. This study will certainly give more support for its use here. A companion study looked at the side effects reported by women in the SOFT study. It found that, overall, those who received ovarian suppression along with tamoxifen experienced more hormone-related issues, like hot flashes, and had more problems with sexual functioning than those taking tamoxifen alone. The difference between the two groups was most apparent at two years, but by five years, both groups were doing about the same. When looking at global quality of life, the study found no difference among the three groups. Blocking a cell pathway may not do what we think it will do. Some women with estrogen positive breast cancer become resistant to hormonal drugs. Laboratory studies using cancer cells and animal models and some small clinical trials led researchers to think this was because the tumors had a mutation that activated what’s called the PI3K pathway. This made researchers think that blocking this pathway could be an effective treatment, leading to the phase II FERGI trial that was reported at the meeting. The study enrolled postmenopausal women with ER+ tumors that had stopped responding to an aromatase inhibitor. They were randomly assigned to receive the PI3K inhibitor pictilisib (which is currently being studied in breast and lung cancer) along with fulvestrant (Faslodex), an estrogen receptor antagonist approved for treating hormone-sensitive metastatic breast cancer in postmenopausal women, or Faslodex alone. After following the women for 17 months, the researchers found that disease progression was about the same in both groups. When they looked more closely, though, they saw that women whose tumors were ER+ and PR+ were less likely to have their disease progress if they had received pictilisib and Faslodex instead of Faslodex alone. (This was a very small number of patients though.) More interestingly, they found that women with PI3K+ tumors did about as well as women with PI3K-negative tumors—which means the drug didn’t work the way they thought it did. So, everyone is going back to the drawing board to figure out how it does work. Overall, there were no big surprises unveiled in San Antonio this year. What I did see, though, were important findings that will be the building blocks of better research. When it comes to cancer treatment, one size does not fit all, and more is not always better. San Antonio 2014 got us one step closer to figuring out which targeted therapies are best for which patients. It also reminded us that our duty is not only to find new treatments but also to determine which breast cancer patients can avoid the toxicities of chemotherapy or radiation, and do just fine. I’ll have more from San Antonio, covering the hottest new developments in breast cancer immunotherapy, in my next blog post.

 

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