Thursday, October 4, 2012

Making sense of the new information on breast cancer.

Last week, the cancer news was kind of exciting and broadcast widely. I heard it on the radio, read about it in the newspapers, and saw it on television. A huge consortium of scientists had looked at the genetic makeup of breast cancers from around 500 patients. They were able to distinguish four kinds of breast cancer that were distinct on the basis of their genetic makeup (these were rough categories and there were divisions within them). The first kind (#1) was the simple bread and butter cancer, typical of post-menopausal women. It responds to treatment with estrogen blockers, and is typically cured with surgery and estrogen blocking with perhaps chemotherapy for some. The next kind (#2) is similar to this one in that it looks like it will respond to estrogen blocking. But, it has some bad features in its genetic makeup that suggests it is less curable by surgery and estrogen blocking. This may also be the kind we see in postmenopausal women, but we can’t be sure. The investigators didn’t give us any clinical information about these women. But, these differences may explain why some women with seemingly curable cancers aren’t cured. Their genetic makeup is different. Another kind (#3) is the kind that contains the growth factor HER2. It can be treated with an antibody to the HER2 that can be curable (usually along with chemotherapy). Finally, there is the baddest actor of them all, the so-called triple negative breast cancer (#4). It is typically found in black women and those with the commonest inherited breast cancer. It does not respond to either estrogen blocking or the antibody to HER2. That is the major reason (not poor health care access) that causes black women to have poor outcomes with their breast cancer. Only chemotherapy works and not that well. In fact the investigators found that these cells were more like ovarian cancer cells another tough cancer to treat. So how does all this information help? It turns out that each of these types is associated with genetic mutations specific to the type. Some of these mutations may be responsible for the growth of the cancers even after they are treated with what we think is the right drug for that type. If we can find drugs that attack these mutations, then we can cure more women. For example, in the estrogen sensitive but not always curable type (#2) if we can find a drug or drugs to attack the other growth promoters along with the estrogen blocking, we may cure more women with this cancer. The same is true for the HER2 type (#3). Adding another drug to the antibody may cure more women. Number one (#1) is usually cured so it is unlikely more drugs will help much and number 4 (#4) will take a lot of research before we can get to it, because for now, nothing helps much. But when I speak of cure, I’m not talking about the woman who has the cancer in her bones or liver or lung. I’m talking about the woman who has surgery to remove the breast cancer and perhaps some cancer-containing lymph nodes. This is the group that can be cured with drug treatment – before the cancer becomes widely disseminated. Once it has spread widely, cure is rarely if ever possible. But all this will take time and, it won’t be cheap. Indeed it may be very expensive if every woman’s breast cancer has to undergo this kind of genetic analysis to find the key to its treatment. And the drugs that target the genetic markers will also be costly. But they may be life-saving.

1 comment:

Greg Pawelski said...

People will think because they are being completely genotyped, this will give all the answers needed. But it won't. Genotyping will only be of value for drugs for which a gene mutation is informative -- basically KRAS and EGFR mutations -- and we already have tests for those and they are of very limited value. Otherwise, it's a ton of information for which the drug selection value is pretty darn useless.

What's more important than what genes are in the DNA is what genes are actively making RNA, which RNA is actively making protein, which protein is being turned off or turned on, and how all of the proteins in the cell are interacting with each other. The only way to get the latter information, which is ultimately what you want, is to treat the patient with phenotype analysis. In drug selection, phenotype analysis doesn't dismiss DNA testing, it uses all the information, measuring the interaction of the entire genome, to design the best treatment for each individual.