WEDNESDAY, MAY 15, 2000

"Integrating Research and Individual Patient Preferences into Optimal Decision-Making for Breast Cancer Treatment"

This evening's Forum took place at Summit Hospital, Oakland. Joining Dr. Tripathy were Lisa Bailey, M.D., breast surgeon and Larry Streiff, M.D., medical oncologist.

DT: The more ancient forms of medicine tailor their treatments to the individual in ways that modern regimens do not. We are learning that there is much variation at the protein and genetic level of the individual tumor which will affect the way a given therapy will work. So although it is important to take the current information from clinical trials, it is most important that it be integrated with the patient's individual profile. The question is how can we minimize uncertainty and best predict the outcome to make the best decisions on patient care.

LS: It will be most important to target our treatment more exactly, to get away from the "lead pipe" approach.

LB: The training I received was "one size fits all". Everyone had mastectomy. Today we are learning more about the disease and involving patients in the decision-making.

LS: This becomes more complicated for the patient as she is more aware of choices that can and must be made. There is also more ambiguity since more options are available but often with incomplete information.

DT: HER2/neu is a good example of this. This oncogene is a good marker, but probably doesn't change treatment options for most people. New information always goes through a period of uncertainty before we know how to use it properly.

Why don't physicians offer rationale for the choice of treatment, say CMF or AC? The rationale should be based on the characteristics of the tumor, but will vary with the patient. The choice should not be a menu, but carefully chosen according to the needs of the patient. AC would not be a good choice for someone with myocardial heart disease. We can give numerical estimates as to which treatment has the best chance of working, balanced against the side effects, but it is still an individual choice. We can use background on clinical trials to refine estimates about benefits, but that is in a population setting, it doesn't mean that any given individual will derive the same benefit. We also must include personal preference. The most important part of communicating all this information to the patient is repetition. It is very difficult to absorb all of the information given in one session.

The doctor should take the responsibility for organizing the visit, so that there is not an overload of information given in the last 5 minutes. Patients also don't hear everything that is being said (tape recorder is valuable), so laying out an agenda is important. We have started a consultation planning service at UCSF. Before meeting with the doctor, an experienced staffer helps to outline what the issues are, so that the time with the physician is more productive and likely to achieve the goals the patient wants to achieve. Internet and literature search is useful. Many patients like to educate themselves and become their own advocate.

What about the genetic component of breast cancer? Only about 10% of breast cancers are genetically determined. Two genes have recently been discovered (BRCA1 and BRCA2) which, when mutated, can pass on a fairly high risk of breast and ovarian cancer. We are not yet sure what to do with this information. The test allows others in the family to know whether or not their risk is high, and it may help with decision making as to whether or not to consider prophylactic surgery. Acquired genetic abnormalities can be found with a particular tumor. Changes occur within the breast either before or after developing cancer; they cannot be passed on to progeny. Genetic abnormalities of this type can be measured through proteins. The first of this protein to be discovered was the estrogen receptor gene (ER) which is highly predictive as to response to hormone therapy. HER2/neu oncogene mentioned previously may also help to stratify risk.

Excluding the very sophisticated and knowledgeable, isn't this information gathering a burden for most patients? This is highly individual, with a lot of variation. Some patients can read the medical literature as well as most physicians while some don't want to be involved in decision-making at all. A physician must listen to the patient, as well as know when to say "I don't know". The trend for increasing amounts of ownership of medical information and decision-making by the public has been trailblazed by breast cancer. Insurance plans are becoming more complicated and the burden of understanding one's medical situation will be shifted more to the consumer. This trend started with HIV and has now moved to breast and prostate cancer. The internet is a great resource: the NIH websites in particular are very good, patient-friendly, and informative (http://www.nci.nih.gov); also http://www.cancerlinks.com.

Since many people are diagnosed through mammograms, what about information at this level, before seeing the oncologist? Although a relatively short delay doesn't increase the risk of someone's cancer spreading, it is certainly very difficult emotionally to have to wait weeks for a physician to discuss diagnosis and options for treatment. Certainly general information should be made available at mammography centers, at the very least, providing public awareness as to where patients might go for general breast cancer information. At the Breast Care Center we try to prioritize appointments for patients with suspicious mammograms for this reason.

What does one do if they are not comfortable with the first oncologist they have seen? If you have a primary care physician with whom you are comfortable, ask for his/her help. Someone who knows you and knows the medical community is vastly better than getting a recommendation from a friend or the phone book.

What do you say to women whose hormone status (HER2/neu, ER, PR) has changed? The results can change in a woman over time, but also the assays are very variable. About 20-30% of the time, if you re-biopsy someone the estrogen receptor can go from positive to negative, especially if you are on hormone therapy. If you are already on a treatment course that seems to be working, there is no need to change the treatment unless the clinical picture has changed, i.e., a progression. A repeat test is in order if the physican feels that the test wasn't done right or the tissue wasn't preserved properly. HER2/neu tests will become more standardized in time, but never perfectly standardized. They don't seem to perform well in the middle ranges. A better gene based assay, Florescence In Situ Hybridization, or FISH, where you can actually look at the copy of genes, is a more definitive test.

What about p53? P53 encodes a protein that is important in many cellular processes, telling cells to stop growing. Cells that continue to grow beyond their programmed limits can increase the aggressiveness of cancer. It is also important in apoptosis, or programmed cell death. Cells need to know when to die, when their usefulness is no longer evident.

Are there any new tests for diagnosing early stage breast cancer? Clearly mammography is the prototype for testing for early stage breast cancer. We are looking at MRI and blood tests, but to date there has not been a test that surpasses mammography. Testing for a recurrence is a different matter. Early detection of recurrence by chest x-ray or serum assay, as opposed to waiting until a symptom develops, does not seem to confer any benefit of time gained. Serum markers can also have their problems, as when they report a false positive. No one will be treated with an elevated marker, with no indication of metastasis in their scans. The major determinant of outcome is not the timing but the nature of the cancer, and whether it will be responsive to the drugs used.

Can metastatic cancer be cured? Permanent cure is not very common, but metastatic cancer is very treatable. Some people will have remissions that last a very long time. With chemotherapy, one has to consider the benefits of therapy balanced against the side effect of the treatment. What we need are more non-toxic drugs like Herceptin which delay the time to progression without causing noxious side effects. A goal is to turn cancer, like HIV, into a treatable chronic disease rather than a killer.

Are the cumulative effects of radiation from screening mammography harmful? To date, there is no evidence of this, but whatever harm there might be is clearly outweighed by the benefit of early detection. In younger women, under the age of 25, high levels of radiation can be carcinogenic in the breast, but this has never been demonstrated in diagnostic levels. There is also very little, if any, data which suggests that suppressing the immune system (with chemotherapy) will increase the incidence of breast cancer or breast cancer recurrence.

Are there any ongoing trials with Herceptin for women with early stage cancer and positive nodes? One is open right now, an NSABP trial for HER2 positive tumors, another will be opening in about a month. The protocol will be Adriamycin/Cytoxan followed by Taxol plus or minus Herceptin.