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U-M CCC - Progress Newsletter Winter 2004 Online

From Genetics to Diet to HRT: Your Breast Cancer Questions Answered

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Cancer breeds questions. At the U-M Comprehensive Cancer Center, we face tough questions every day - in our clinics, our laboratories, our classrooms and our community - and we know we're only as good as our latest answer. To address some of these questions we hear most often, we've created FAQ, a new feature in Progress. In this first installment, Daniel Hayes, M.D., Clinical Director of the Breast Oncology Program, responds to some Frequently Asked Questions about breast cancer.

Should I undergo genetic testing to assess my risk?

Here at Michigan, we're fortunate to have a clinic devoted to Breast and Ovarian Risk Assessment, headed by Dr. Sofia Merajver, to provide not only testing, but the counseling necessary to help women navigate this question. But before readers rush to make an appointment, there are a few key points to keep in mind: Genetic abnormalities (such as those in BRCA1 or 2) account for only 2 to 5% of all breast cancers -- in other words, 95% of breast cancers are not related to genetic mutations. And for the average woman (without a very strong history of breast cancer in her family), her chance of testing positive for a mutation is less than 1%. A full cadre of genetic testing is expensive, and there is a risk of tests resulting in "false positives” -- indicating a defect when none is present. Finally, it is not clear that every abnormality will lead to cancer.

Considering all of that, who would proceed with testing?

We don't recommend testing as a standard first step. First, we try to determine whether a woman falls into a high-risk group. Women with a family history of breast cancer in two or more first-degree relatives (parents or siblings), breast cancer striking a family member before age 40, or occurring bilaterally (in both breasts), or a family history of ovarian cancer would fall into that group. Risk increases when more than one of these factors is present. Again, family history is not necessarily a reason to proceed with testing. Our genetic counselors are the experts at helping determine the right course of action.

Can I make lifestyle changes to reduce my risk of developing breast cancer?

Unfortunately, no one has yet identified a specific diet that reduces risk or helps treat breast cancer - but not from a lack of trying. Many scientists do think weight and nutrition are linked to breast cancer though, and they trace that link back generations.

Over the past several hundred years, our western world has shifted from an agrarian to an industrial base. Over that time, we”ve seen a change in women”s reproductive patterns. The average age of a woman”s first menstrual period was around 15; today it is around 11. The age of her first full-term pregnancy has shifted from her late teens then to her late 20's or older today. She bears fewer children today, too, and no longer relies solely on breast feeding. And the average age of the onset of menopause has shifted from her 40's then to her 50's today.

What does all of this history have to do with breast cancer? It's a fact that the earlier a woman's first menstrual period, and the later her first full-term pregnancy, the greater her risk of developing breast cancer.

The major risk factor impacted by this seismic shift is the production of estrogen. Alone, the presence of estrogen doesn”t predict breast cancer, or all women would have it. But in combination with other factors, the promotion of cellular turnover by growth factors like estrogen ultimately leads to breast cancer.

What does this have to do with our weight? The final pathway of estrogen production is through fat cells. So, long story short -- maintaining a healthy weight by making smart nutritional choices and exercising will help to moderate estrogen production and, we think, reduce breast cancer risk. We also believe alcohol changes estrogen metabolism and increases circulating estrogen levels. So keeping consumption to a minimum is another smart lifestyle strategy. As for smoking, although it”s not as strong an indicator as it is for lung cancer, it remains an incredibly bad idea. Even if we can”t prove quitting lowers your risk of breast cancer, you should still quit.

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What is the link between post-menopausal hormone therapy and breast cancer?

For years we have suspected that women who take hormone replacement therapy (HRT) had a higher chance of getting breast cancer. However, until recently, HRT was believed to offer the following benefits when employed after the onset of menopause:

1. minimizing hot flashes

2. reducing the risk of osteoporosis

3. helping guard against heart attack and stroke

4. improving cognitive function

5. reducing the appearance of facial wrinkles

But reports from recent randomized clinical trials suggest that HRT may actually worsen cognitive responses, and, at least in the short term, increase the risk of heart attack. So, although HRT clearly helps with hot flashes and osteoporosis, these newly-identified red flags make it a less attractive option. One alternative researchers at U-M and elsewhere are pursuing is the use of anti-depressants to offset the impact of hot flashes. The research looks very promising. As for osteoporosis, the best bets remain calcium supplements (1000 mg/day), moderate exercise and smoking cessation.

Is there a link between birth control pills and breast cancer?

I'd estimate that there have been about 25 clinical studies addressing this question; 1/3 suggest the pill increases risk, 1/3 indicate it has no effect, and 1/3 suggest it decreases risk. Without conclusive science, we're left to judge. Unlike HRT, which is replacing lost estrogen, birth control pills are used to increase or regulate estrogen from already "normal” levels. Therefore, for most women, barring other risk factors, I believe the risk posed to be minimal.

Is it true there's a new blood test that can detect breast cancer?

No. Would I like one? Yes. The challenge is developing a test that's incredibly accurate to avoid the consequences of false positives.

Let's do the math: Today in the U.S. roughly 240 of every 100,000 women over 40 will be afflicted with breast cancer. If you had a test that was 90% sensitive and 90% specific, and administered it to 100,000 women, you would identify approximately 200 cases, but you would also have 10,000 false positives. That's why randomized clinical trials are so important -- to make sure that whatever we bring to the public -- every new test and new treatment -- offers far more benefit than potential harm.

If I am diagnosed with breast cancer, can I pursue a breast-sparing strategy, or is it safer to just have a mastectomy?

We now have the benefit of six randomized clinical trials confirming that breast conserving therapy has equivalent outcomes to mastectomy, so that's pretty well established. A significant number of our patients are still better served by mastectomy, but that's based on their risk of in-breast recurrence. We explore every option with them before proceeding down that road. It's interesting that in the U.S., mastectomy remains the treatment option pursued in about 50% of cases. We think that reflects "over-treatment”, but the choice ultimately resides with the patient.

Recently, a study was published about the use of the drug letrozole (Femaraª )to prevent breast cancer recurrence for patients who have taken tamoxifen (Nolvadexª) for 5 years. Are you using letrozole with your patients at U-M?

Letrozole is one of a class of new drugs called aromatase inhibitors (AIs) that inhibit the activity of an enzyme that converts estrogen-precursor molecules into estrogen. These drugs are used for patients who have metastatic disease even after tamoxifen is not working.

The study you refer to, and others, suggests that AIs may complement or even replace tamoxifen to prevent recurrence. But a note of caution: We know a lot about the long term effects of tamoxifen, but far less about these agents. The small added benefit of AIs compared with tamoxifen may not outweigh the risks. Only more time and information will help sort this out. In the meantime, we agree with the American Socieity of Clinical Oncology (ASCO) -- they recommend tamoxifen as the drug of choice for adjuvant threatment of women with estrogen receptor-positive breast cancer. AIs are appropriate for select women for whom tamoxifen is not indicated. The recent study suggests that starting letrozole after five years of tamoxifen might be better than no further therapy. But again, we need to be cautious. In general, these patients have favorable prognoses. We should be certain that the benefits of absolute reduction of estrogen levels outweighs the risks Ð such as increased risk of osteoporosis.

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