This is gleaned from a telemedicine lecture from Virginia Mason in Seattle, Washington on October 19, 2009.

Screening for Breast Cancer in High Risk Women

In any woman alcohol does increase breast cancer risk, if there is more than two ounces intake daily. I tell people they can't save up for the weekend. 1.5 increase in relative risk. To put it in perspective, more than 2 ounces of alcohol is a risk equivalent to a first degree relative (mother, sister, daughter) with breast cancer.

Re MRI. There's a lot of battling going on at the research level about when to do an MRI for many reasons:

--high cost
--variable technique
--imperfect specificity
--patient barriers: size of patient/kidney function/claustrophobic
--questionable survival benefit

Virginia Mason (VM) has established a protocol for use of breast MRI. The recommendation for a breast MRI is that it be used for high risk patients as defined by:

--BRCA 1 & 2. Last year I learned that these are protective genes and it is their absence or mutation that causes the problem.
--> 20% risk (Gail model risk calculator)
--radiation to the chest age 10-30 (usually for another cancer)
--Li-Fraumeni (TP53 mutation) or Cowden (PTEN mutations)I had not heard of either of these genetic risks for breast cancer before. More on breast cancer genetics.

For high risk patients, MRIs should start at age 30, except for the inherited genetic problems, which should start at age 25 or 5-10 years younger than the youngest affected family member.

There is built in discrimination, in that MRI is so expensive, that only those with "good" insurance will get one. MRI is not being withheld from low risk patients: it really isn't helpful because they are not always easy to read and you can get false positives that lead to biopsies that make the person higher risk.....

Testing for BRCA 1 & 2 mutations is sometimes covered by insurance, and costs around $3700. My employer was changing insurance companies and the old one did cover $3200, while the new one didn't at all. I did the testing and paid $500. I have offered it to patients and have never had one agree; I found it hard to do and hard to go in for the results.

Studies are examining breast cancer genetics and mRNA expression of 16 genes. They have developed a recurrence score, divided in to low, medium and high. It gives an estimated breast cancer % recurrence over the next 10 years. 51% of node negative patients are low score and then do not need adjuvant therapy (such as tamoxifen, chemotherapy or radiation). People with high scores have a 27% recurrence rate over 10 years, so adjuvant therapy should be given. They are doing randomized trials of the intermediate scores -- either tamoxifen alone or tamoxifen and chemotherapy.

Tamoxifen is metabolized to endoxifen. However, 10% of patients are poor metabolizers. There is a Roche test of CYP2D6 (known as sip2-D-6) for $300 to identify poor metabolizers. Fluoxetine (prozac) and paroxetine (paxil) sometimes mess up the metabolism of tamoxifen by inhibiting CYP2D6 and shouldn't be used with it. Tamoxifen is being compared to other aromatase inhibitors. Hot flushes turn out to be important -- there are less in the tamoxifen non-metabolizers. Thus the doctor will be cheerful if the woman has hot flushes on tamoxifen, because they are likely to have a "better outcome". This is really getting in to "personalized medicine" where the genetics of an individual are guiding treatment. It is called molecular profiling.

There are arguments going on about whether the Gail Model high risk calculator is better than the genetic testing. Virginia Mason currently recommends doing genetic screening if the life expectancy is 5 years or less.

Inflammatory breast cancer requires an MRI. It turns out that inflammatory breast cancer cells can become sensitized to tamoxifen sometimes by estrogen. So even though we don't use hormones in people with breast cancer, there might be a small group where we do. It makes the cells hypersensitive to the tamoxifen.

That's what I got from the lecture. It is confusing, isn't it? Remember that we used to only diagnose stage III and IV breast cancer, so that is where the best studied treatments are. I have patients with early breast cancer who are offered 3-4 alternatives and want to know which is BEST. The truth is that it's all under study and is changing every year. I predict that there will be more and more genetic testing in the future, to direct treatment. I do worry that it will become impossibly expensive and complicated to treat even a hangnail. Doctors are in the unenviable position of being sued for doing too much OR too little. Let's all strive for perfection at all times.