June 2007: Updates from ASCO 2007

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Herceptin and Tykerb effective for HER2+?

Question from Heather: Have any studies been done comparing the effectiveness of Herceptin and Tykerb in the treatment of HER2-positive breast cancer, and if so, what are the results?

Answers —Nicholas Robert, M.D.: There has been a small study with pertuzumab and Herceptin. There was some benefit seen. Using other drugs like pertuzumab with other drugs like Tykerb is an area we're studying. I'm not aware of any particular studies at this time of that combination.

Generosa Grana, M.D., F.A.C.P.: Most of the data that's currently available on Tykerb is from patients who have failed prior Herceptin therapy.

Updates on treatment for triple-negative?

Question from Twink: I was diagnosed in January with triple-negative breast cancer. I don't often read promising news regarding treatment of this type of cancer and would like to hear whether there's anything hopeful on the horizon for us triple-negative types. Also, I did read that carboplatin/cisplatin seems to show better survival results for triple-negative breast cancer; could the expert guests elaborate on that subject?

Answer —Nicholas Robert, M.D.: The category triple negative should be thought of as a group of tumors that are negative with our standard tests, but probably positive for other variables we don't know yet how to measure. There is work being done to understand the biology of so-called triple-negative tumors. In the meantime, there was a study showing the patients that are triple negative benefit from a regimen that contains weekly Taxol. There is also some work that is very preliminary, evaluating cisplatin (brand name: Platinol) and carboplatin (brand name: Paraplatin) in triple-negative breast cancer. At this point, it's too early to see whether these two agents will have a role in this cancer category.

Trials successful for HER2 vaccine?

Question from Eileen: Have any of the clinical trials for a HER2 vaccine proven successful?

Answer —Nicholas Robert, M.D.: There was a presentation at the San Antonio Breast Cancer Symposium in December 2006 with preliminary information suggesting that in a group of women that has HER2-positive breast cancer, there were some potential benefits of the vaccine. The study was small and will need to be expanded to see if there is truly a benefit.

What drugs in latest cancelled study?

Question from Ninnj: What drugs were in the latest study that was canceled?

Answer —Generosa Grana, M.D., F.A.C.P.: There has been a study in the planning stages for women with increased risk of breast cancer comparing Evista (chemical name: raloxifene) to letrozole. While tremendous enthusiasm surrounded this study, and it was a continuation of much work that has been invested in prevention of breast cancer, the NCI has not seen fit to fund the trial. Currently, other sources of funding are being sought and we will yet have to see if this trial will go forward. There is going to be data on the use of aromatase inhibitors in the prevention setting. A trial currently being done in Europe, IDIS II, will give us such information. As of yet, the only drug FDA-approved for prevention is tamoxifen. There is data (although no FDA approval) for Evista in post-menopausal women. And there is no data on the aromatase inhibitors in a prevention setting.

Other bone metastasis medications?

Question from Terese: Are there any new clinical trials or new targeted treatments for bone metastases that has just barely spread from breast cancer, other than Zometa and Faslodex?

Answer —Generosa Grana, M.D., F.A.C.P.: There is an interest, although no data as of yet, looking at agents such as Quadramet (chemical name: Samarium Sm-153 lexidronam) in this setting. This agent, which is a radioactive compound that is delivered intravenously and focuses on bone, has traditionally been used in women with bone metastases and pain. Currently, there are studies looking at this drug in addition to Zometa (chemical name: zoledronic acid) and we shall see where that research leads us.

SSRIs impact on tamoxifen efficacy?

Question from Linda: Good evening, doctors. Would you please share the latest info on the impact of SSRIs (specifically Zoloft) on tamoxifen efficacy? Is there a test that will show how well a person is metabolizing tamoxifen? This information does not seem to be widely circulated.

Answer —Nicholas Robert, M.D.: This question raises a very important aspect of treatment, which is how different people metabolize the same drug differently. There is now an understanding that tamoxifen can be metabolized different ways, depending on what enzymes people have. In addition, there are certain drugs that can inhibit enzymes and will also affect the metabolism. At this point, everyone is trying to figure out how to use this information in recommending drugs like tamoxifen. There is now an understanding that SSRIs do affect tamoxifen and should be avoided if tamoxifen is to be used. There is also the ability to do a blood test to determine how well tamoxifen is metabolized, but it remains unclear how to use this test when recommending tamoxifen. This area will need to be studied in greater detail before we can make firm recommendations.

New breast cancer genes found?

Question from Ranz: What new genes have they found in breast cancer with family history?

Answer —Generosa Grana, M.D., F.A.C.P.: The reality is that the only two genes that are commercially available for testing are BRCA1 and BRCA2. A gene known as CHEK-2 has been reported to account for a very small percent of hereditary breast cancer, well less than 1 percent. Work on a third or a fourth gene, the AT gene (which stands for ataxia telangiectasia gene) is also ongoing and may play a role in a very small component of hereditary breast cancer. Commercial testing for these two latter genes is not yet available. For the majority of women that have a strong family history and test negative for mutations in BRCA1 and BRCA2 we clearly need more research done to clarify the factors contributing to their cancer. About 30 percent of women with hereditary breast cancer based on family history criteria will test negative for mutations in BRCA1 or BRCA2. There are other genes that appear to be much more frequent in the population that individually account for small increases in breast cancer risk, and a lot of work is ongoing to understand their role.

News on breast cancer biomarkers?

Question from Ugen: Is there any news on breast cancer biomarkers?

Answer —Nicholas Robert, M.D.: There has been for some time the observation that you could measure in the blood so-called tumor markers, and these have included CEA and CA 27-29 or CA 15-3. More recently there has been the observation that one can identify circulating tumor cells. Another test is measuring part of the HER2 proteins. All these tests so far have only had some benefit in patients with metastatic breast cancer. And even in that situation, some of these tests can be negative. In patients who have early breast cancer, the so called adjuvant study, there is not any effective blood test to identify patients who may have micro-metastases. There is now new technology which permits us to measure very small amounts of proteins in the blood, the so-called nanotechnology, but so far a blood test has not been identified that helps in patients with early breast cancer.

Role of anthracyclines in treatment?

Question from NancyJ: Could you comment on the NBC news segment by Robert Bazell about research by Dr. Dennis Slamon presented at this conference? Included in the news segment is the statement: "The anthracyclines—with all their side effects—have almost no effect in 92 percent of breast cancer cases." It goes on to say this is "exciting news." Well, not for thousands of women (including myself) who have had chemotherapy!!!

Answers —Nicholas Robert, M.D.: The role of anthracyclines in breast cancer in both metastatic disease and in the adjuvant setting represented a very positive step in the treatment of patients. However, over time, we are beginning to understand better the benefit of anthracyclines. There is some evidence that suggests that patients with HER2-positive breast cancer may not need to be treated with an anthracycline, and even patients who are HER2 negative may also not need to be treated with anthracycline. There is work being done trying to identify those patients who may not need to be treated with an anthracycline. The biology relates to an enzyme Topoisomerase, which is abnormal in a majority of breast tumors. It may be that this is the only group that truly benefits from anthracycline. However, much work needs to be done to see if this is true.

Generosa Grana, M.D., F.A.C.P.: For a large number of women, anthracyclines are still routinely utilized. So until we have more information for large numbers of women, anthracyclines are used in the treatment of early stage disease either with agents such as Cytoxan (chemical name: cyclophosphamide) or with the taxanes. Dr. Slamon's research will hopefully let us identify the appropriate patient population that will most benefit from these agents.

Nicholas Robert, M.D.: We—that is, US Oncology Network—have currently initiated a clinical trial where we are treating a group of patients with a regimen that does not include anthracyclines versus a regimen that does to see if we can omit anthracyclines in some patients.

Latest on treatment and memory loss?

Question from JSmith: What are the latest developments regarding memory loss resulting from drug therapy for cancer? Any hope on the horizon? Particularly, is there any recovery, either partial or complete, from such memory loss? I'm speaking about short-term memory loss, but long-term loss could be an issue. Thank you.

Answer —Generosa Grana, M.D., F.A.C.P.: I think it has long been recognized that memory loss and other cognitive defects are seen in the setting of cancer treatments. They are seen with chemotherapy, hormonal therapies, and with the combination. How much of this is due to the actual chemotherapeutic agents and the supportive drugs given with chemotherapy, and how much is due to the onset of menopause and other factors has yet to be determined. The encouraging news is these symptoms tend to get better over time, although that time frame can be one year or longer.

Recurrence rates for MammoSite vs. 3D Conformal?

Question from Aliceb: How do the recurrence rates for MammoSite Radiation and 3D Conformal Radiation compare at this point in the clinical trials for each?

Answer —Generosa Grana, M.D., F.A.C.P.: The trial that is currently ongoing comparing whole breast conformal radiation to MammoSite has not completed accrual and is still ongoing, so no data is available from this national trial. There is data from smaller institutional trials with limited follow-up, suggesting that MammoSite has good effectiveness at preventing recurrence of cancer in the breast and has good cosmetic outcomes. For now, multiple organizations have suggested that it is imperative that this trial be completed and that patients whenever possible be enrolled on this trial, so that the data will become available.

Less invasive reconstruction techniques?

Question from Tweetie: Are there any less invasive reconstruction techniques being developed any time in the near future?

Answers —Nicholas Robert, M.D.: There is some interest in so-called subcutaneous mastectomies that will preserve the nipple area. However, the different techniques for reconstruction that have been developed using a free flap are usually more time consuming and would not be described as less invasive. In terms of implants, there is an increasing experience of using silicone implants versus saline implants, which may produce a better cosmetic outcome, at least in the opinions of some.

Generosa Grana, M.D., F.A.C.P.: The choice of reconstruction has to be individualized to the body habitus of the woman, the size and the extent of the breast cancer, and the potential use of post-mastectomy radiation. But we have made significant advances in breast cancer reconstruction.

Replacement for AC cocktail?

Question from AmyG: Now that it's been established that AC chemotherapy only benefits women with a specific gene, or 8 percent of breast cancer patients overall, will women be tested for that gene? Will AC be replaced by another chemo cocktail in the near future? Thanks!

Answer —Nicholas Robert, M.D.: There is already evidence for replacing AC chemotherapy with TC chemotherapy, where T stands for Taxotere (chemical name: docetaxel). The reason to consider TC is that this appears to be more effective than AC without some of the toxicity associated with the anthracycline. However, in some patients, knowing whether the topoisomerase gene is abnormal means that there still may be a role for AC. This still needs to be evaluated with prospective clinical studies to make sure that we're measuring the right gene and identifying which patients benefit or not from AC.

Information on AMG 706?

Question from GGT: I just started a clinical trial in Australia for AMG 706. I have secondaries in my liver. Do you have any info on this drug, and if not, what are the latest treatment options for liver secondaries? I have also investigated SIRT—Selective Internal Radiation Therapy.

Answers —Generosa Grana, M.D., F.A.C.P.: Although not actively familiar with this particular compound, the approach to women whose breast cancer has spread to the liver varies, depending on whether that is the only site of disease, and how many lesions are present in the liver. Or whether there are other sites of involvement, such as lungs and bones. Liver-targeted therapies, such as chemoembolization, or other strategies targeting the liver can be utilized in women that have a small number of lesions (two to four lesions). For other patients, systemic chemotherapy may be more appropriate.

Nicholas Robert, M.D.: Regarding the use of AMG 706, this is an agent that affects blood vessel formation and like the drug Avastin (chemical name: bevacizumab), which is another agent that uses a different mechanism, but may provide a similar benefit. I would encourage patients who are eligible for the study to participate. This is how we learn about better ways to treat breast cancer.

Vitamin D as prevention agent?

Question from Fava: There have been some scientific presentations on the efficacy of Vitamin D as a possible breast cancer prevention agent. What is your take on this and if favored, what are your recommendations as far as daily supplemental intake (in the form of tablets)? Some are saying as much as 1,000 IU/day. Thanks.

Answer —Nicholas Robert, M.D.: There is some information on the benefit of the use of Vitamin D. At this point, it's not clear that the evidence is definitive. However, in postmenopausal women who are at risk for osteoporosis, there is a good argument to use Vitamin D, as much as 800 IU/day. Of course for preventing osteoporosis one should also use exercise and calcium.

Studies on bioidentical hormones?

Question from CWald: Have there been any studies on bioidentical hormones for breast cancer survivors?

Answer —Nicholas Robert, M.D.: We don't have enough information to comment. Sorry. Keep watching Breastcancer.org for more information about new research as it becomes available.

Under 35, strong family history?

Question from WSH: I'm a breast cancer survivor and a mammographer. What guidelines are being used for recommendations for women under 35 who have a strong family history of breast cancer?

Answer —Generosa Grana, M.D., F.A.C.P.: The recommendations that have been put forth were first published in JAMA and are in the process of being updated. While these recommendations support the use of mammography beginning at around 25 years of age for women with hereditary risk, there is no conclusive evidence as to the true effectiveness of this approach, or any potential long-term risk. Women with the mutation BRCA1 or BRCA2, or from families that meet the criteria for hereditary disease but where no mutation has been identified, are also recommended MRI of the breast as an ancillary screening tool. There is data demonstrating that MRI enhances the pick-up rate of mammography in such a population. Digital mammography is ideally suited for women who have a strong family history, are young, and have greater breast density. The definition it provides enhances the detection of breast cancer in this population. More and more facilities in the United States are converting to digital equipment, so it should be more commonly available.

Ovarian ablation vs. chemo for early stage?

Question from UUY: Is there any new information regarding disease-free survival using adjuvant ovarian ablation rather than chemotherapy for early stage breast cancer?

Answer —Nicholas Robert, M.D.: There is no new information. This approach continues to be a subject for clinical trials to identify the specific role of ovarian ablation either with the drug tamoxifen or aromatase inhibitors.

Long-term side effects of AIs?

Question from Magri: Is there any news on the long-term side effects of the aromatase inhibitors?

Answer —Generosa Grana, M.D., F.A.C.P.: The data that is available and that was reviewed at ASCO looked at potential toxicities from two of the trials using letrozole, although there is data from presentations looking at the other aromatase inhibitors. Data from the BIG 1-98 trial suggested slightly greater cardiovascular risks with letrozole over tamoxifen, but significantly less clotting risk. The ideal situation is to try to identify patients based on risk/benefit analysis. We also know that all of the aromatase inhibitors cause some degree of arthritic complaints and have a negative effect on bones, increasing risk of osteoporosis. Despite this, these drugs are very effective for the treatment of hormone-receptor-positive early stage breast cancer, and have some features that make them much more desirable than tamoxifen in the same population.

New hormonal drugs for estrogen positive?

Question from Niet: For women who had a lot of hormonal therapy drugs (estrogen positive) in the beginning of illness, are any new hormonal drugs available?

Answers —Nicholas Robert, M.D.: In patients with early breast cancer who are post-menopausal, there is evidence for using hormonal therapies for periods longer than five years. This initially was demonstrated with using letrozole in women who had been treated with tamoxifen for five years. When given letrozole, patients had a reduced risk of recurrence. This observation has led to an interest in using aromatase inhibitors earlier in the treatment of patients with breast cancer, but also an interest to see if this type of hormonal treatment should be given for a longer period of time. There are ongoing studies asking this question.

Generosa Grana, M.D., F.A.C.P.: In metastatic disease, the most recently studied hormones have been Faslodex (chemical name: fulvestrant). It is an active compound and no new data has been presented recently on this compound. There has been some interesting data presented in Europe and San Antonio, combining aromatase inhibitors with Herceptin in women that are both HER2-positive and estrogen receptor-positive. Studies are ongoing, combining other aromatase inhibitors with some of the newer targeted therapies, such as lapatinib.

Results from Oncotype clincial trial?

Question from JeanM: Are there any early results from the Oncotype clinical trial reducing the intermediate score for chemo to 11?

Answer —Generosa Grana, M.D., F.A.C.P.: That trial is currently ongoing across the country. In that trial, the scores were changed slightly so that low-risk is considered a score less than 11, intermediate risk is 11 to 25, and high risk is greater than 25. The rationale for changing the score to these levels was to optimize the treatments for early stage breast cancer and to allow maximal use of aggressive therapy. No data will be available for some time on this trial.

DCIS treatment with ER, PR negative?

Question from LizA: I'd like to know if there are any new research findings on DCIS treatment, especially for the patient with ER, PR negative.

Answer —Nicholas Robert, M.D.: I'm not aware of any new research regarding the treatment of patients with DCIS where the hormone receptors for estrogen and progesterone are negative. Interestingly, some of these DCIS tumors are positive for HER2, raising the question of whether an anti-HER2 strategy can have any potential benefit, especially now that we have an oral anti-HER2 drug. At this time, the role for such an approach would be speculative but there may be in the future an interest in exploring this approach. The question does raise the role of local management of DCIS regardless of estrogen/progesterone status. There was data showing the benefits of using radiation to reduce the risk of local return in patients who were treated with lumpectomy for their DCIS.

New tests for IBC?

Question from BETTY: Are there any new tests concerning the redevelopment of inflammatory breast cancer?

Answer —Generosa Grana, M.D., F.A.C.P.: Our approach to inflammatory breast cancer (which was initially to treat it aggressively with chemotherapy, surgery, and radiation) is the same as for all other forms of breast cancer. We rely on physical exams and careful evaluation of patients for symptoms of recurrence. There is no more use of scans and markers in these patients than in other patients with Stage I or II breast cancer.

Sleep aids for breast cancer patients?

Question from Beth: I have a very difficult time sleeping through the night due to side effects of treatment and my worries. Are there any sleeping aids that were discussed specifically for breast cancer patients?

Answer —Generosa Grana, M.D., F.A.C.P.: A variety of sleeping aids are used for women undergoing treatment for breast cancer. None of them are specific to women with breast cancer. The important factor is to recognize when sleep difficulty may be due to menopausal effects, i.e., insomnia might be caused by night sweats that are due to the onset of menopause. If this is the case, treatment of menopausal symptoms with compounds such as clonidine (brand name: Catapres), Neurontin (chemical name: gabapentin), or the SSRIs may be beneficial rather than just focusing on standard sleep aids.

Most potential in breast cancer research?

Question from Claudette: If you could wave a wand and fund research in any area for a future ASCO, what would it be? Where do you see potential?

Answer —Nicholas Robert, M.D.: That's a great question—it asks where we think the future in breast cancer management will be. First, a better understanding of the genes that play an important role in breast cancer development. The story as we begin to understand it is complicated, but we are beginning to appreciate that there are numbers of genes that need to be recognized that increase the risk of developing breast cancer. Further areas of study would be the genes and proteins that play roles in the actual breast cancer. We are learning more and more that there are different genes and proteins in different breast cancers, recognizing these different patterns could give us potential insight on how an individual cancer may behave and more importantly, give us a better idea on how to treat an individual breast cancer. There is even a potential with a better understanding of the biology of the breast cancers that we could develop better prevention strategies.

Advances in the next 5 years?

Question from BFur: Where do you see breast cancer in the next 5 years?

Answer —Generosa Grana, M.D., F.A.C.P.: I see a better approach to the identification of who ultimately needs treatment for early stage disease, and what treatments may be ideal for that particular patient. We have started on that pathway with data presented on Oncotype for lymph node-negative women. Clearly, similar technology will be utilized to more broadly approach other populations with breast cancer and to help us determine, not only whether to treat with chemotherapy but with what specific chemotherapeutic agent. We will also see a better understanding of the pathways involved in breast cancer progression and metastasis, and develop drugs specifically targeted to these various pathways. We have seen, for example, in this last ASCO meeting, much work done unraveling the HER2 pathway and we have 3 or 4 potential drugs targeted to this specific pathway. This is but one of the multiple pathways in the cell that will ultimately be targeted to improve outcome.

Does media relay research accurately?

Question from Xino: What role does the media play in supporting or misreporting the work being done by researchers? How do we, as consumers and patients, know what to believe?

Answer —Nicholas Robert, M.D.: This very important question tries to address the issue of news that is what I would describe as hard to believe it's really true, and doesn't recognize the reality that progress in breast cancer management is incremental and takes time. The challenge is to unravel the mystery of breast cancer biology and this is not easy to do. When hearing a story from the media, it's important to listen carefully to see if this information is speculative or represents the result of a clinical trial that usually involves large number of patients. The devil is in the details and it is organizations like breastcancer.org that are very helpful in providing guidance and informing people what is really new and effective.