December 2004: Updates from the San Antonio Breast Cancer Symposium

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Aromatase inhibitors for pre- vs. post-menopause?

Question from KimG: Hello! There has been a lot of discussion regarding aromatase inhibitors and their use in post-menopausal women. I am still premenopausal (age now 36), hormone- receptor positive, and have been on tamoxifen for 4 years. Are there any new studies showing benefit for inducing menopause (oophorectomy) and switching to an aromatase inhibitor once I have reached the 5 year mark of tamoxifen? Thank you for your response.

Answers —Generosa Grana, M.D., F.A.C.P.: It is a challenge knowing what to do with the premenopausal woman who is facing the five-year completion point of tamoxifen. There's no data yet available on the use of aromatase inhibitors in premenopausal women. European doctors are doing a study on ovarian suppression, plus tamoxifen or Arimidex. The only data available from that study is on the effect on bones. There is no data on the effect of these approaches on breast cancer recurrence, which is what we need to focus on.

In the 35 year old woman, I think the issues should go back to whether genetic testing has been done. If there is a reason to remove the ovaries, then you'd have a reason to put someone like this on letrozole (Femara). In the premenopausal women facing this decision, I think it's appropriate to go back to genetic testing to help determine whether that should be given consideration.

Marisa Weiss, M.D., president and founder: It's also reassuring to know that the benefit of five years of tamoxifen lasts longer than the actual five years that you're taking the medication. This is called a carryover effect. If you are noticing irregularity in periods on completion of your five years of tamoxifen, and you go through menopause a year or so later, it's still worth asking your doctor about the possibility of starting an aromatase inhibitor, like Femara, at that time.

Generosa Grana, M.D., F.A.C.P.: The key to your taking an aromatase inhibitor is feeling confident that you're in complete menopause. That confidence comes from either not having a menstrual cycle for a year or longer, and confirmatory data can be drawn from laboratory studies. In a premenopausal woman where you're concerned about the true status of her menopause, it is a very reasonable approach to proceed with blood testing.

Osteoporosis prevents from taking Arimidex?

Question from Patti: I can't take tamoxifen due to family history of strokes and blood clots. Arimidex is the recommendation for me, but I have osteoporosis. Is there a solution for me? Thank you.

Answer —Generosa Grana, M.D., F.A.C.P.: The effect of the aromatase inhibitors on bones is well recognized. They tend to exacerbate bone loss and increase fracture risk. By simply having osteoporosis, it doesn't mean a woman can't use an aromatase inhibitor; rather, it means her osteoporosis needs to be managed aggressively and followed closely.

So in a woman who has preexisting osteoporosis where you very much want to use an aromatase inhibitor, you would try the oral bisphosphonates, such as Fosamax or Actonel. By following the bone density on repeated DEXA scans, you can see if these oral therapies are working.

If they're not, then intravenous drugs such as Zometa can be instituted and given 2 to 3 times per year. I would say that several clinical studies are currently ongoing, using agents such as Zometa to prevent the bone loss that occurs with the aromatase inhibitors. Data from those studies should help us handle these issues better in the future.

Can hormone receptor status change?

Question from Jams: Can a person's hormone receptor status change from negative to positive if because of treatment you are put into permanent menopause? If so, how can one verify this? I would like to take hormone therapy but cannot as I am hormone receptor negative and not having periods.

Answer —Generosa Grana, M.D., F.A.C.P.: The only cases of a change in hormone receptor status of a tumor have been in women who have had recurrences of their cancer, and there are times when the cancer recurrence is different from the original cancer when it comes to estrogen receptor and progesterone receptor status. But that is unusual.

Celebrex can prevent recurrence?

Question from Judy: Did Celebrex show promise for preventing the return of cancer in ER/PR negative patients?

Answer —Generosa Grana, M.D., F.A.C.P.: There are several studies focusing on cancer treatment and prevention with Celebrex, a COX-2 inhibitor. The data as it exists is very preliminary, based on animal studies, and one cannot recommend Celebrex for treatment or prevention of breast cancer in any population. There is a study being done in women with early stage breast cancer where Celebrex is being studied, but that study is just now accruing patients, so we are not ready to make any recommendations based on that.

Femara after tamoxifen for node negative?

Question from Mgoodman: What is the latest recommendations for women who are finishing tamoxifen after 5 years? If they were node negative, should they consider Femara?

Answers —Generosa Grana, M.D., F.A.C.P.: The data from a study published this past year suggests that node negative and node positive women who are postmenopausal, hormone receptor positive, and completing five years of tamoxifen would benefit from the addition of letrozole (Femara) for an additional five years. However, only in the node positive population do we see a true survival advantage. We do see a decreased risk of recurrence in all women, so it is reasonable at this point to discuss with the oncologist whether this is an appropriate strategy for every woman. Every oncologist and patient will base their decisions on the initial characteristics of the cancer, the woman's age, and the woman's other health problems, not just the data that was presented.

Marisa Weiss, M.D., president and founder: At this time, we only have three years worth of follow-up on the women who took tamoxifen for 5 years, followed by Femara. Women in this type of study generally have a favorable situation, as they were still doing fine 5 years after treatment, and they were postmenopausal with hormone receptor positive disease. Women in this study are likely to live a long time. So in order to learn from them, and to see the whole effect of each treatment, we need to follow them for a long time as well. Over the years, as this study matures, expect to find out more important lessons to be learned that can help you make your subsequent decision and have a better idea in the long term.

How long does healing take?

Question from Marie: I had 11 lymph nodes removed (7 positive) and finished radiation October 16. Part of my chest is still very sore (some days very painful). Am I still in the healing process? Or is this a chronic condition that breast cancer patients get?

Answer —Marisa Weiss, M.D., president and founder: It takes a significant period of time to heal after all the treatment that you've had. The armpit is a particularly difficult area to heal from after surgery and radiation. Most of the acute skin changes—like redness, swelling, and tenderness—improve significantly over the first month or two after treatment.

Some of the nerve-related discomfort can take a lot longer to go away, however. After the nerves have been cut during surgery, they tend to "go to sleep," resulting in numbness. Eventually, the nerves wake up and get upset about all the changes that have happened to this part of the body. When they start to function again, they can cause uncomfortable feelings like crawling, itching, burning, and shooting discomfort. Eventually, these seem to improve.

If you have difficulty with range of motion, flexibility, and strength in that area, ask your doctor to send you for a physical therapy consultation. During the period of time you have discomfort, try to learn how to improve it with changes in activity, lotions, and medication. Things are likely to get better for you.

Treatment for ADH better than tamoxifen?

Question from Faye: I am taking tamoxifen for atypical ductal hyperplasia, and a friend mentioned to me there is a new treatment that is better than tamoxifen. If so, what are the benefits and are the results better than taking the tamoxifen? Thank you.

Answer —Generosa Grana, M.D., F.A.C.P.: Atypical ductal hyperplasia (ADH) is an abnormal accumulation of cells within the ducts of the breast, and this is the marker of increased risk of breast cancer. There is currently no data in the setting of prevention (which is what we are doing when we are treating a woman with ADH) to support using anything other than tamoxifen. Tamoxifen was tested in a large study that included women with ADH, and it reduced the risk of recurrence by 50% in the general population, and 85% in the group with ADH.

The data on the aromatase inhibitors that we have seen presented at San Antonio in no way addresses prevention. The data we have seen is purely in patients with breast cancer. The Europeans are studying aromatase inhibitors for prevention of breast cancer, so there is a large study comparing a placebo pill to Arimidex in high risk women. There also was a study completed in the United States comparing tamoxifen to Evista (raloxifene) in high risk women such as those with ADH, but no data is yet available from that study. So for the moment, women such as this are offered either observation or tamoxifen.

Hormone therapy vs. radiation after lumpectomy?

Question from Ann: Please discuss hormone therapy and the possibility of not doing radiation in postmenopausal women after lumpectomy. I have had one positive node removed as well. Thank you.

Answers —Marisa Weiss, M.D., president and founder: Regardless of your age, you deserve the best treatment possible, and the only way to do that is to get the best care from each specialty. This includes radiation if it is appropriate in your situation. In general, the standard of care is to treat the whole breast. This can be done by removal of the whole breast, called mastectomy, or removal of the lump followed by radiation to the remainder of the breast tissue.

For women with a small cancer that is completely removed without lymph node involvement, partial radiation may be appropriate using a specialized device. In early 2005, the NSABP will start a study that will take women with a single site of breast cancer up to 3 cm with no lymph node involvement, and randomize them between two treatments for full breast radiation versus partial breast radiation.

If you are a healthy women who is likely to live at least five years or more, then you are likely to benefit from radiation. Radiation can reduce the risk of local recurrence by two thirds.

Generosa Grana, M.D., F.A.C.P.: In the very elderly and women in poor health, this can be discussed with the radiation therapist, but in general, all women should discuss the benefits of radiation therapy.

Marisa Weiss, M.D., president and founder: Chemotherapy or hormonal therapy or both are not as powerful as radiation at reducing the risk of local recurrence. It is the combination of each of these therapies that gives you the lowest risk of recurrence.

How risky is pregnancy after treatment?

Question from Anati: How risky is it to get pregnant after breast cancer? How many years should I wait? I am 37 — two years now after treatments.

Answers —Generosa Grana, M.D., F.A.C.P.: The effect of pregnancy on breast cancer recurrence is poorly studied. There is no data available thus far that shows that women who choose to become pregnant increase their risk of recurrence or bad outcomes from their breast cancer, nor do they seem to be at increased risk of poor outcome of the pregnancy.

What is important is to discuss the timing of pregnancy with the medical team to optimize the management of the breast cancer, and the results of the pregnancy. But there is no set amount of time that a woman should wait that can be absolutely recommended.

If the woman is estrogen receptor negative, and no hormonal therapy is going to be utilized, then there is less of a rationale to wait longer. While if the woman is hormone receptor positive and hormonal therapies are part of her treatment, it may be advisable to wait after taking tamoxifen.

Marisa Weiss, M.D., president and founder: For more information about planning for your future as a parent with respect to fertility concerns and juggling your breast cancer treatment, please see our section on fertility and pregnancy.

How long to be on Aredia/Zometa?

Question from Elizabeth: Was there anything at the conference about the length of time someone should be on Aredia/Zometa? I have been on it for almost seven years with good results. My doctor gets blood chemistry monthly and everything is normal except for a slightly elevated BUN, which doesn't change much month to month. Is there anything else we should be looking at to monitor kidney function or any other possible long-term side effects?

Answer —Generosa Grana, M.D., F.A.C.P.: The duration of Aredia or Zometa in women with bone involvement from breast cancer is unknown. Traditionally, women have been placed on these drugs when the bone metastases have been diagnosed, and are continued indefinitely. Your doctor is appropriately concerned about the effects on the kidney, and is doing the recommended evaluation, which is checking the creatinine monthly.

Recently there have been reports of remarkably rare complications seen with the use of these compounds, called osteonecrosis of the jaw. This is usually seen in women and men who have had dental procedures or removal of teeth while on these drugs, and the sockets don't heal and can cause significant problems. We don't know what predisposes women to this, or how big an issue it really is. So for now, most clinicians are not using this as a criteria for stopping treatment or cutting the drugs short.

The bisphosphonates that are used intravenously, Aredia and Zometa, are also being investigated for individuals who don't have advanced breast cancer, but may have osteoporosis or bone loss caused by either the onset of menopause with chemotherapy, or the onset of menopause with ovarian blockage. So in the future, women may be using these compounds for a variety of reasons.

Should having two cancers affect treatment?

Question from Mgoodman: I had 2 bilateral stage I cancers. Both were node negative. I have had 5 years of tamoxifen, no chemo, and my ovaries out. Based on one cancer, I don't think I should now take Femara. How much should the fact that I had these two cancers affect my decision?

Answers —Generosa Grana, M.D., F.A.C.P.: The fact that there were two cancers should not affect the decision to use or not use Femara. The prognosis for any patient is not additive, but rather depends on the worst cancer that occurs. The decision to use Femara should also be considered in the setting of whether mastectomy was done or not. If you have had bilateral mastectomy, it would lessen my inclination to use Femara.

Marisa Weiss, M.D., president and founder: Sometimes we feel that more treatment is better than less. You've done a lot of therapy so far to reduce your risk of developing breast cancer in the future. Beside taking medication, it's important to become as healthy as you can be - eating well, sticking as closely as possible to your ideal body weight, and exercising regularly can all help you feel well and improve all aspects of your health.

Differences between aromatase inhibitors?

Question from Garsar: Please explain the differences between the three aromatase inhibitors in terms of treatment and side effects. Also, is there any problem taking Herceptin at the same time? Thank you.

Answer —Generosa Grana, M.D., F.A.C.P.: There are currently 3 aromatase inhibitors on the market — Arimidex (chemical name: anastrozole), Femara (chemical name: letrozole), and Aromasin (chemical name: exemestane). Femara and Arimidex are non-steroidal compounds, meaning their structure does not resemble the chemical structure of steroidal hormones. These two compounds bind to the aromatase enzyme in a reversible fashion. In reality, that means that their activity depends on the concentration of drugs and enzymes. Aromasin, on the other hand, is a steroidal compound and it actually has a chemical structure that looks a bit like the structure of the male hormones, the androgens. It also binds to the enzyme in an irreversible fashion and does not let go.

There is no clinical data to date that suggests that these different structures or these different ways of binding actually affect clinical outcome. The side effects of these drugs are similar, so there's no great suggestion that the differences of structure or function lead to a different side effect profile. More work needs to be done to study these compounds and there are studies currently ongoing that are comparing these compounds in early stage breast cancer.

Editor's Note: In October 2004, the FDA approved Femara for extended adjuvant use in women with early-stage, hormone-receptor-positive breast cancer after five years of tamoxifen. In October 2005, the FDA approved Arimidex for adjuvant use in women with early-stage, hormone-receptor-positive breast cancer. Also in October 2005, the FDA approved Aromasin for use as adjuvant treatment in women with early-stage, hormone-receptor-positive breast cancer after taking two or three years of tamoxifen.

Natural progesterone helpful for ER+?

Question from Kagee: Is natural progesterone helpful or harmful if you have estrogen receptor positive breast cancer?

Answer —Generosa Grana, M.D., F.A.C.P.: The effect of progesterone on breast cancer is not well known. In the Women's Health Initiative which looked at hormone replacement in postmenopausal women, the women who got combined estrogen/progesterone had a slightly increased risk of breast cancer. The women who received just estrogen did not have as much of an increase in risk. So there is a concern about what progesterone's role is in breast cancer.

Also important is the fact that we have very little information on what "natural progesterone" really does and how it's different from synthetic progesterone. Much of the information available on this is available only from cell culture studies, rather than true human studies. So I cannot truly endorse widespread use of this. It's something that should be discussed with the oncology team involved in your care.

Future of treatment options?

Question from Tracey: Where can you see us 5 or 10 years from now for different treatment options?

Answers —Marisa Weiss, M.D., president and founder: Pull out your crystal ball!

Generosa Grana, M.D., F.A.C.P.: I think it's a very exciting time for breast cancer. There are many things in development that are likely to mature into real treatment options for women. We have a lot of excitement around what are known as "targeted therapies", agents such as Iressa, Avastin, Lapatinib and others. Targeted therapies are treatments such as Herceptin which are aimed at a target within the cancer cell that has been identified. Tamoxifen is a targeted therapy because it binds the estrogen receptor. Herceptin has as its target the HER-2/neu receptor.

Much of the excitement in breast cancer will come from a better understanding of the very complex pathways involved in the development of cancer. In the past, we focused all of our attention on the estrogen receptor, and later the HER-2/neu receptor. We're beginning to understand that insulin and the insulin growth factor receptors are going to be important. There are many other pathways we need to understand so we can develop better therapies.

The other improvement over the next 5 to 10 years, I believe, will be that we'll have better ways of predicting who needs treatment because they are at increased risk of recurrence, and who is not because they have a good outcome. For the women who need treatment, we need tools to determine which treatments are most effective.

There has been much discussion since San Antonio about what to do with the "recurrence scores." This is referring to testing that can be done on the tumor specimen that was removed from the patient. A panel of 21 genes can be tested for in the tumor and the pattern that evolves can then be put together into a score. Two studies have shown that the score in certain populations may be helpful to predict outcome from breast cancer and may also be helpful to predict effectiveness of treatment.

But we have to be careful that we understand what the studies look at. The two studies were in women that had early stage breast cancer, T1 or T2 (meaning under 5 cm, or about 2 inches) but most women had significantly smaller cancers than 5 cm. They were all hormone receptor positive, and they were all part of clinical trials.

In one study, women received tamoxifen or a placebo, and in that study it was shown that women who had a low recurrence score fared well, and women who had a high recurrence score did not fare as well with just tamoxifen. In the other study, which included women who either got tamoxifen or chemotherapy plus tamoxifen, women who had a low score or an intermediate score did well with just tamoxifen and did not get much benefit from chemotherapy, whereas women with a high score got great benefit from chemotherapy. These are tests that are beginning to be incorporated into clinical practice, but many people feel there is so much uncertainty about how to best use these tests.

Marisa Weiss, M.D., president and founder: Can you tell us what you think is most important about diagnostic testing?

Generosa Grana, M.D., F.A.C.P.: I thought the most interesting was the data on MRI in high-risk women or women who are at hereditary risk of breast cancer. These women have a high risk of developing breast cancer, as high as an 85% lifetime risk. The data is now building to show that MRI when compared to clinical breast exam, mammography or ultrasound, is better at detecting cancers and can detect them at a smaller size when treatment is likely to be less difficult and the outcome is likely to be better. Studies are being done offering women free MRI if they meet certain criteria, and I encourage women to register for these tests if they are eligible.

Marisa Weiss, M.D., president and founder: Was there important information presented about the role of prophylactic mastectomy?

Generosa Grana, M.D., F.A.C.P.: There was important information about prophylactic mastectomy for women who are at hereditary risk. The data falls along the lines of what we saw from previous studies done at the Mayo Clinic. Clearly, prophylactic mastectomy decreases the risk of breast cancer in high-risk women (women who carry a mutation in the BRCA1 or BRCA2, or who come from a family of multiple cases of breast or ovarian cancer that by definition are considered hereditary, but where a mutation has not been identified.)

I would add that the message from these studies is not that prophylactic mastectomy is for every woman, but all high-risk women should be aware of the option and should be able to make an informed personal decision.

Marisa Weiss, M.D., president and founder: I was pleased to see that the information presented on sentinel lymph node dissection showed fewer side effects.

Generosa Grana, M.D., F.A.C.P.: The data from the large European trial and data also from an American trial showed that sentinel lymph node biopsy, allowing us to avoid full dissection of the lymph nodes under the arm, can be done with less shoulder problems and less long term shoulder and movement issues than we traditionally see. This is very encouraging for women.

Can oopherectomy prevent recurrence?

Question from Grits: How beneficial is an oophorectomy in preventing a recurrence?

Answers —Generosa Grana, M.D., F.A.C.P.: The true benefits of oophorectomy (removal of the ovaries) in preventing recurrence is still being debated. Studies in Europe show that oophorectomy, or blockage of the ovaries using Zoladex or Lupron, is associated with a significant improvement in outcome from breast cancer. Use of this plus tamoxifen is also effective, at least as effective and maybe slightly more effective than chemotherapy with CMF. Whether it will be just as effective as the newer chemotherapies that are currently in use in the United States is not known.

Women in Europe are much more likely to be recommended ovarian removal or suppression as part or all of their cancer treatment. In the USA, this occurs less frequently. There are 2 important questions being addressed by clinical trials now — one asks how good is ovarian suppression, and second, should it be combined with tamoxifen or with aromatase inhibitors? Furthermore, can it be done with or after chemotherapy? So there is still much debate as how to use it. We know breast cancer is amenable to hormone changes, so we know it works. How best to use it is less clear.

Marisa Weiss, M.D., president and founder: Were there important presentations addressing women with hormone receptor negative disease?

Generosa Grana, M.D., F.A.C.P.: There was not much new in terms of other strategies, other than chemotherapy. There was an excellent review of women with lymph node positive breast cancer, looking at the three last large chemotherapy trials that were conducted in the United States. Interestingly, the benefit of advances in chemotherapy in those trials was seen more in the women who were estrogen receptor negative The women who were estrogen receptor positive did not get as much benefit from chemotherapy.

Advice on bone loss after treatment?

Question from Chat: My doctor has me on Aromasin and Actonel. I have some bone loss issues after 6 months of chemo and 6 weeks of radiation. Anything I can do after the fact to help with the bone loss, other than Actonel weekly and calcium tablets?

Answer —Generosa Grana, M.D., F.A.C.P.: I think you are doing the things one would recommend — calcium, vitamins, and the Actonel are effective. Also exercise plays a part. Avoid smoking, since that's associated with bone loss. The other important thing is monitoring the bone density over time. We know Actonel is very effective, but if you see continued bone loss, you may be one of those women who may be appropriately treated with the more potent intravenous drugs such as Aredia and Zometa.

Side effects with Effexor, Lupron, tamoxifen?

Question from Lisa: I am currently taking Effexor, along with Lupron and tamoxifen. I had once read that there are possible side effects using Effexor with these drugs. Is this true?

Answer —Generosa Grana, M.D., F.A.C.P.: Many people utilize Effexor to improve the menopausal symptoms that can be brought on by Lupron and tamoxifen. It can help the hot flashes, night sweats, moods. To date, I'm not aware of detrimental interactions. There have been reports of an interaction between tamoxifen and Paxil, another antidepressant of the SSRI class.

Okay to take vitamin E for menopause?

Question from Lisa: I have been taking 800 mg of vitamin E to reduce the menopausal side effects - is this okay? Some recent studies have been published saying that people should not be taking high doses of Vitamin E so I did try stopping it, but felt a big difference.

Answer —Generosa Grana, M.D., F.A.C.P.: Neither the benefit nor the detriments of vitamin E have been established. Studies have looked at vitamin E to treat hot flashes, and they did not show anything above what the placebo effect would show. Yet obviously you are getting benefit from it, and that's important. Nobody has a real good handle on whether vitamin E is protective or harmful in terms of breast cancer risk. In addition to that, we don't know what dose is safe or is not safe. With my patients, I discuss the use of vitamin E if it's symptomatic, and keep the dosage as low as possible, but again, it's somewhat of an unknown.

Cost of Arimidex lowering?

Question from Darlene: I am pleased to be taking Arimidex. It is extremely expensive. Is there any hope for a price lowering in the future?

Answers —Generosa Grana, M.D., F.A.C.P.: That's a very important question. Although the aromatase inhibitors are more effective than tamoxifen, can add to the benefit of tamoxifen, and have fewer side effects than tamoxifen, the down side is that they are quite expensive—around $220 dollars a month which can be a lot for people with no health insurance. I don't foresee a decline in the price of these drugs.

Relief will come in 2 ways: one, through a national prescription drug coverage to help patients, and secondly, the plans that the different pharmaceutical companies provide to give free drugs for individuals with financial need. Some plans are very flexible, so you may be able to take advantage of them.

Marisa Weiss, M.D., president and founder: Try shopping around. You may find the lowest prices available at Costco or a discount pharmacy closer to you. There can be significant price variation between drug stores.

Brachytherapy prevents recurrence?

Question from Rain: How effective is breast brachytherapy in preventing recurrence in premenopausal women, or anyone?

Answers —Marisa Weiss, M.D., president and founder: For women with early stage breast cancer, they may be presented with a choice between full breast radiation or partial breast radiation after lumpectomy when the whole cancer is removed with clear margins. Brachytherapy, which is the slow delivery of radiation to a specific area, is one way to deliver partial breast radiation. An increasingly popular approach is to use a special balloon device called a MammoSite. This uses high dose radiation. Radiation is given using the balloon catheter twice a day for 5 days in a row for a total of 10 treatments. This has been available on a special registry.

Several thousand women have been treated with this approach over 3 years. The risk of recurrence is extremely low during this period of observation. Again, in early 2005, there will be a randomized study called NSABP B-39. If you or someone you know is interested in participating in this study, contact your doctor.

Generosa Grana, M.D., F.A.C.P.: I think the most critical thing from the conference was the data around the use of aromatase inhibitors. Data was presented on starting Arimidex at once, supporting its use. Data was presented from 2 trials, switching patients from tamoxifen to exemestane, showing better effectiveness. So clearly the use of the aromatase inhibitor and how to incorporate them into clinical practice is one of the most challenging thing facing oncologists today.

I found the information presented about newer regimens of chemotherapy to be so early. There was nothing presented with respect to chemotherapy that was as groundbreaking as the dose-dense data presented last year, or the TAC data presented a year ago. Both of these continue to be excellent regimens for women with node positive disease. There was much information presented on combining different chemotherapies, combining Herceptin with other therapies, but none of those had dramatic results.

Hormonal therapies and lipid, triglyceride levels?

Question from Jen: What is the current data on the effect of tamoxifen, Arimidex, and Aromasin on lipid and triglyceride levels? I have been on tamoxifen for 18 months and mine keep increasing. Should I change to another estrogen suppressor?

Answer —Generosa Grana, M.D., F.A.C.P.: The data on the effects of hormonal therapies on lipids is rather small. There have been case reports of hypertriglyceridemia, or elevated triglyceride levels with tamoxifen, although it does not happen often. There was a study presented a year ago that compared tamoxifen and the other aromatase inhibitors in terms of the effects on lipids, all showing not a dramatic effect on lipids. But again, this is based on small numbers of patients and short follow-ups, so I can't say there are big differences in lipid effects between these agents. So discuss with your doctor the treatment for cholesterol. I'm not certain that changing from one hormone to another will make a big difference.

Avastin and miltefosine for skin metastases?

Question from Eddie: My wife is battling HER2+ inflammatory breast cancer four years, underwent various chemos, radiation, radical double mastectomy. She has it in the bones and as IBC on her chest. She's on Zometa and Herceptin. I need your opinion on Avastin and miltefosine (Miltex) [for skin metastases].

Answer —Generosa Grana, M.D., F.A.C.P.: Clearly, inflammatory breast cancer is a very aggressive form of breast cancer. These cancers tend to present with rapidly growing disease in the breast, and the typical finding is redness, swelling, and puckering of the breast that has occurred rather rapidly. Although these cancers can be effectively treated, they do have a higher risk of recurrence, and your wife is now dealing with both the threat of the cancer to the bone as well as the local problems of the inflammatory disease in the chest.

The approach to these patients is problematic, although she is lucky her cancer is HER2+ because Herceptin is a great option. It can be used alone or with a variety of chemotherapy agents. I am not aware of the agents that you asked about, but Avastin is actively being investigated in breast cancer as are other agents, such as lapatinib.

These drugs, including lapatinib, are currently under investigation and may be available in the next two years. While these drugs are currently undergoing testing, you should look into clinical trials that may make these agents available to her. The National Cancer Institute may have such trials, or local institutions closer to your home may have active trials with these compounds.

Advice on increasing bone mineral density?

Question from Jules: Since beginning Femara, my bone mineral density has significantly decreased and I've had several fractures despite using Fosamax, taking calcium, Vitamin D and doing weight bearing exercise. What would you recommend? What do you feel about Forteo?

Answer —Generosa Grana, M.D., F.A.C.P.: Unfortunately, the effect of the aromatase inhibitor on bones is very real. Loss of bone mineral density with these agents is well established. You are doing all of the things that one would recommend, which include calcium and vitamin D, and clearly this is not enough. At this point, I tend to refer women to a rheumatologist or endocrinologist because there are other tests that should be run on a woman who is not responding as expected and continues to have bone loss and fractures, despite effective treatment. After all possible things are tested for, one can consider using agents such as Aredia for this.

Forteo (chemical name: teriparatide) is a new compound that is used for the treatment of severe osteoporosis. It is a parathyroid hormone. Its use should be discussed with an endocrinologist or rheumatologist, and its use is individualized. Other drugs that can be used for osteoporosis include Miacalcin (calcitonin-salmon), although this tends to be weaker than the other bisphosphonates. There are some interesting compounds currently in development that may really change our approach to bone loss.