Today I went to the NBC studios toÂ do an interview with Brian Williams for his Nightly News show. We talked about what a new study, published today in the New England Journal of Medicine, tells us about how best to use chemotherapy to treat breast cancerâ€”and why the more we learn about tumors the more we learn about which chemotherapy benefits which tumor types.
Whatâ€™s crystal clear is that the treatment of breast cancer is growing up. Initially all women were treated the same, one size fits all, and we were glad to save a few lives despite of the side effects of the therapy. Then we figured out that some tumors were sensitive to hormones and some were not, and that only those that were responded to hormone manipulation. More recently, a test called Oncotype DX has been developed that allows us to distinguish which women with ER-positive tumors will benefit from chemotherapy and which will notâ€”and thus donâ€™t need it.
The second significant determinant of treatment was Her2 status, which tells us who will benefit from Herceptin and who will not.
The study I spoke with Brian Williams about looked at 1500 women with node-positive breast cancer who had taken in part in a study in the 1990s that had randomly assigned them to receive doxorubicin (brand name Adriamycin) plus cyclophosphamide (brand name Cytoxan) followed by four cycles of paclitaxel (brand name Taxol)â€”the regimen commonly referred to as AC followed by T.
The researchers were able to get samples of these womenâ€™s tumor tissue, which had been frozen and saved, to analyze it for HER2 status. (Herceptin had not yet been approved and tumors were not tested for HER2 status when this trial took place.) They found that women with HER2 positive tumors benefited from paclitaxel, regardless of their estrogen status. However, women with HER2-negative, ER-positive breast cancerâ€”the most common type of breast cancerâ€”gained little from having paclitaxel added to their chemo regimen.
The researchers are encouraging other scientists to look at past Taxol studies and to see if these also show that HER2 status makes a difference. This is significant because, obviously, not only do we not want to give women a drug that they wonâ€™t benefit from, but because Taxol frequently causes neurological side effects, such as numbness and tingling in the hands and feet that can last for months or years after treatment ends. Another recent study published in the Journal of Clinical Oncology gives us even more information about which chemotherapy is best for women whose tumors are HER2-positive. This study showed us that within the HER2 category there are women whose tumors also overexpress another gene that is called Topo II. This group of women (about 8% of women whose tumors are HER2-positive) apparently does best when they get chemotherapy that includes an anthracycline, like Adriamycin, as well as Herceptin. In contrast, women whose tumors are HER2-positive but donâ€™t also overexpress Topo II do just as well with a non-anthracycline drug.
Why is this important? Anthracyclines are known to cause cardiac damage, some of which can show up even long after the treatment is over. Adding Herceptin to Adriamycin compounds this damage, and so identifying women who could use an alternate combination is important in limiting the consequences of treatment. In addition it may be that women with HER2- negative tumors could use another drug, like cytoxan that has less long-term effects on the heart.
We are entering a new stage in breast cancer treatment, where we have choices. Since there are 2.4 million women living with breast cancer the long-term effects of therapy should be important in determining the best choice!
What does this mean to a woman newly diagnosed? She should get a second opinion about her chemotherapy treatments. She should ask questions, not only about what the benefits of the treatment will be but also the risks and whether there are alternative treatments that might have less long-term side effects. Many doctors are creatures of habit and we sometimes need to jolt them out of their routine to get them to incorporate the latest data into their practice.