I was really disturbed when I heard the news this morning. There were two big Symposium-related stories.Â One of these stories was based on a poster that will not be presented until Saturday that addresses the use of estrogen alone to treat menopausal symptoms. The other, which will not be presented until later today (Friday afternoon), is on zoledronic acid (brand name zometa) and breast cancer recurrence. This means that what was in the paper and on the news on Friday morning was based on press reports put out by the authors and on data that participants at the meeting had not yet been able to evaluate.
My comments, therefore, are on the estrogen alone study press release and abstract.Â Basically, this study is a reanalysis of the estrogen-alone arm of the Womenâ€™s Health Initiative.Â This arm has already been reported as showing an increase in breast cancer. In addition, other studies have shown that it may take longer to see the effect from estrogen only than it does from a combination of estrogen and progesterone.
As you read the media reports, it is important to remember that the estrogen-only arm of the study enrolled only women who had undergone a hysterectomy (removal of the uterus). These are the only women who can take estrogen alone, as doing so can increase the risk of uterine cancer. What we donâ€™t know is how many women in the estrogen-only arm of the study also had had their ovaries removed. This is important information to have because removing the ovaries reduces a womanâ€™s risk of breast cancer by about 70%.
Also, the data reported in the abstract suggested that the only risk reduction was short-term and that it was only in women who did not have a family history of breast cancer or had had a previous breast biopsy. I would be very interested in whether breast density seen on mammogram was also related to breast cancer risk. Unfortunately, I wonâ€™t be able to tell you until Saturday, when we get to see all the data. (As you can probably tell, I do not think this poster should have been singled out to be promoted to the media and, if it was going to be promoted, it certainly shouldnâ€™t have been done until after conference participants had had a chance to see the data!)
This morning (Friday) the first several presentations were on HER2-positive breast cancer.Â These studies evaluated the effectiveness of giving trastuzumab (brand name Herceptin) and two new drugs that also target HER2-positive tumors lapatinib (brand name Tykerb) and pertuzumab with and without chemotherapy prior to surgery to women with large tumors. Giving drugs before surgery (called neoadjuvant treatment) is being done more and more in clinical trials because it allows the researchers to see whether the tumor is responding to the drug. (If the tumor is responding it will get smaller.)
Two of the studies compared Herceptin to Tykerb, and the researchers reported that in both studies Herceptin was more effective. The combination of Herceptin, Tykerb, and chemotherapy had a 50% complete response rate (this means that 50% of the time no cancer was seen at the time of surgery), with women who were estrogen receptor (ER) negative more likely to have a complete response. However, as Dr. Eric Winer, the director of the breast oncology center at the Dana-Farber Cancer Institute in Boston who led the session discussion pointed out, overall, women with ER-positive tumors do better, so whether there is a complete response is only one factor in overall survival.
The next presentations focused on other drugs now in the pipeline for treating HER2-positive tumors. For those of you who have triple-negative tumors, that session is coming! Alan Ashworth, a professor of molecular biology at the Institute of Cancer Research, in London, received an award and gave a good talk on the concept behind the PARP2 inhibitors and some new approaches to finding new drugs.
A surgery session reviewed local treatment and the only new piece of information was that the current trend seems to be either breast conservation or bilateral mastectomy.Â The problem with a risk-reduction mastectomy, though, is that the risk of recurrence from the first cancer is usually higher than the womenâ€™s risk of getting a second cancer in the other breast. Lastly, several papers were presented that updated data on chemotherapy studies. We learned, for example, that TAC (Taxol or Taxotere, Adriamycin, and Cytoxan) seems to be better than FAC (fluorouracil (5FU), Adriamycin, and Cytoxan).
The other study that had been widely reported this morning was on Zometa, a bispohosphonate similar to alendronate (brand name Fosamax) but given IV. Unlike the estrogen-only study, though, this one is very interesting and important.
Initial observational studies (non-randomized studies that compare a group who are taking a drug for whatever reason to a group who are not taking it) had suggested that women with breast cancer who took Zometa had less bone metastases and higher disease free survival. Also, earlier data from an Austrian study had shown that Zometa not only helped prevent bone loss from treatment but also seemed to decrease recurrence in the breast and the bones.
Today, researchers reported data from a much larger European trial, called AZURE, that randomized women with Stage II or III breast cancer to either have standard therapy or standard therapy with Zometa. The study found that there was no improvement in disease-free survival or bone metastasis survival. In addition, there were 17 episodes (1.5%) of osteonecrosis of the jaw in the women who received Zometa. These findings were very disappointing and everyone was trying to figure out why this study was so different from the first one. Much more discussion will take place, but for now we should probably reevaluate giving women Zometa to decrease recurrence.
Lastly, an interesting study was added in at the end of this session. This study (which has also gotten a lot of media attention) looked at how many women in the United States actually got mammograms between 2006 and 2009. The researchers used only fully insured women in the study so that the data would not be influenced by ability to pay. Interestingly, they found that only 57% of women age 40-50 and 65% of women 50-64 were getting annual mammograms. We know women are greatly concerned about breast cancer, and this study show that there are large groups of women who have insurance who could be getting mammograms who arenâ€™t. Now, we need to learn why.