June 2010: Updates from the 2010 ASCO Annual Meeting


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Ask-the-Expert Online Conference

On Thursday, June 10, 2010, our Ask-the-Expert Online Conference was called Updates from the 2010 ASCO Annual Meeting. Andrew Seidman, M.D. and Beth Baughman DuPree, M.D., F.A.C.S. answered your questions about the latest updates on breast cancer risk, screening techniques, treatment options, and more.

Are aromatase inhibitors beneficial beyond 5 years?

Question from Kathryn: I've read that women in other countries with invasive advanced breast cancer (receptor positive) are taking Arimidex for longer than 5 years (10 years) and are having better outcomes -- less recurrence, decreased risk of cancer spreading to other parts of the body, decreased risk of new cancer developing in the other breast. Is this true? Thank you.
Answers - Andrew D. Seidman, M.D. The question regarding the duration of Arimidex (chemical name: anastrozole), an aromatase inhibitor, can be addressed by considering the available clinical trial data. Five years of aromatase inhibitor is currently considered to be the standard in care. We also know that patients who receive tamoxifen can benefit from extended 5-year aromatase inhibitor therapy. We also know that following 2 years of tamoxifen, switching to an aromatase inhibitor for the rest of the 5 years is another option. However, using an aromatase inhibitor beyond 5 years is a question that is currently the subject of a clinical trial, known as MA17R, so currently, extended use of aromatase inhibitor beyond 5 years cannot be considered the standard of care. Having said that, a careful discussion between physician and patient can result in a decision to continue based on careful consideration of the known risk and, to be sure, the unknown benefits.

Empirical studies on breast self-exam?

Question from nea: Have there been any empirical studies on breast self-examination? What is the general consensus?
Answers - Beth Baughman DuPree, M.D., F.A.C.S. Although studies have been published that show that breast self-exam does not benefit patients in the early diagnosis of breast cancer, for women under the age of 40 and for women with very dense breasts, breast self-exam may be the woman's only tool to evaluate herself on a regular basis to increase what I like to call breast awareness. Because 20% of all breast cancers are not found mammographically, breast awareness is something that as a surgeon I believe still has more benefit than harm. Although clinical trials cannot show a specific statistically significant improvement in the diagnosis of breast cancer, it is but one of the tools that a woman has to use in an attempt to diagnose breast cancers as early as possible. Patients should not feel as though not doing a regular exam is right or wrong. I oftentimes feel that educating women about understanding the normal architecture of their breasts is just an important aspect of knowing their own body.

Risk of metastasis in BRCA patients with and without bilateral mastectomy?

Question from Marilyn: Is there specific data re: bilateral mastectomy with regard to BRCA patients versus just lumpectomy? If so, what is the difference in having this treatment with first breast cancer diagnosis? Are the chances of metastasis different in BRCA patients with and without bilateral mastectomy?
Answers - Beth Baughman DuPree, M.D., F.A.C.S. Patients who carry the BRCA1 and 2 mutations are at a significant risk for cancers in the opposite breast after the diagnosis of a first malignancy. That risk is far greater than the general population, and the risk of a woman who carries the BRCA1 or 2 mutation of developing a first cancer is approximately 50% by the age of 50 and 87% by the age of 70. The choice of lumpectomy or mastectomy does not play into the risk of systemic recurrence, as tumor size, estrogen, progesterone, and HER2 status as well as axillary lymph node status will dictate the patient's risk of the cancer showing up some place else in the body.

No woman has ever died of breast cancer in her breast, as breast cancer is only lethal when it spreads to distant areas in the body. One of the reasons why women who carry the BRCA1 and 2 mutation choose bilateral mastectomy prophylactically, meaning before a cancer occurs, is that this population of women with increased risk have what is commonly known as a triple-negative breast cancer. These cancers tend to grow very fast and at this point in time, we do not have a specific targeted therapy that can be given to definitely halt any potential tumor cells from continuing to divide. Women who carry the BRCA1 mutation have approximately 56% of those cancers that are considered triple-negative. The choice of lumpectomy and radiation therapy in BRCA patients is a personal decision that a patient will make, and the risk to the opposite breast for developing a primary cancer in that breast is elevated due to the genetic mutation.
Andrew D. Seidman, M.D.

The only thing I will add, which I think the questioner was trying to address, was whether having a specific BRCA mutation implied a greater risk of systemic disease. I think it's just important that a woman understand, as Dr. DuPree noted, that a patient's BRCA status itself is not a prognostic factor for the likelihood of developing distant metastases. The determinants of that event are, again, tumor size, receptor status, nodal status, and perhaps multi-gene tests such as Oncotype DX and MammaPrint.

Editor's Note: The Mammostrat test is another genomic test approved by the FDA in 2012.

When will the Cleveland Clinic breast cancer vaccine trials begin in humans?

Question from SandyW: What is your opinion about the Cleveland Clinic vaccine? When will trials begin in humans?
Answers - Beth Baughman DuPree, M.D., F.A.C.S. Although it has been used in the laboratory, I do not know when it will begin its work in humans. Continue to watch for updates in the Breastcancer.org Research News section.

Additional research on side effects of lymph node removal?

Question from ASilva: For those who have had lymph nodes removed, is there any research happening in regards to lessening the side effects?
Answers - Andrew D. Seidman, M.D. We actually have a wealth of new data from this year's American Society of Clinical Oncology meeting. There was a study that showed that sentinel lymph node biopsy is indeed a safe alternative to full axillary lymph node dissection when the sentinel lymph node does not contain cancer. This supports what has already become common clinical practice. The sentinel lymph node procedure typically results in less pain and, importantly, less lymphedema.

There was additional provocative data from the ACOSOG Z11 trial that even called into question the role of axillary lymph node dissection at all in patients with a small axillary tumor burden, generally favorable tumors, who underwent breast-conserving surgery. However, it is important to note that this trial fell quite short of its target patient accrual and patients should discuss the possibility of omitting axillary lymph node dissection directly with their breast surgeons.

Editor's Note: Visit Breastcancer.org's Reducing Risk of Lymphedema and Lymphedema Flare-Ups page for more information.

Current recommendations for Femara after surgery and chemotherapy?

Question from LDesign: I have just completed 5 years of Femara for breast cancer (after surgery and chemo). What is the current recommendation for duration to take that drug? I am hoping to be DONE, but understand that research changes over time. Thanks!
Answers - Andrew D. Seidman, M.D. The use of either anastrozole (brand name: Arimidex) or letrozole (brand name: Femara) beyond 5 years cannot currently be considered standard of care. There are known risks with extended use of aromatase inhibitors, but the benefits are underdetermined. An ongoing clinical trial, which is an extension of the MA17 study, will answer this question for Femara.

Updates on denosumab to prevent bone metastases?

Question from Mertz: In light of continuing concerns about long-time use of Zometa in the metastatic setting, was there any update about a possible new drug that might have fewer side effects called denosumab?
Answers - Andrew D. Seidman, M.D. It is an exciting time in our understanding of the biology and treatment and prevention of bone metastases. Denosumab (brand name: Prolia) is an agent that is emerging as a powerful tool against osteoporosis in osteolytic metastases from breast cancer, prostate cancer, and multiple myeloma. While it has a favorable safety profile as the questioner implied, it is not without possible toxicities. It was recently approved by the FDA for treatment of osteoporosis and is considered for its role in treating bone metastases.

News about PARP inhibitors for triple-negative cancers?

Question from MomOf4: Any new news this year about PARP inhibitors for triple-negative?
Answers - Andrew D. Seidman, M.D. While we still await the data from a large randomized Phase III trial evaluating BSI-201, there were several smaller studies reported at this year's ASCO meeting. One study involved the oral PARP inhibitor olaparib, which was administered with weekly Taxol (chemical name: paclitaxel) chemotherapy for triple-negative metastatic breast cancer. (Abstract number 1018 at ASCO.) Another study examined yet another PARP inhibitor, veliparib, in combination with a chemotherapy agent called Temodar (chemical name: temozolomide). In this trial, significant responses were seen in patients with metastatic breast cancer who carried BRCA mutations. Still, to date there are no commercially available PARP inhibitors, and their ultimate role depends upon the awaited results of large randomized trials.

Results from the breast cancer and yoga trial?

Question from ChloeN: Do you have any information about the yoga and breast cancer trial? What did they find?
Answers - Beth Baughman DuPree, M.D., F.A.C.S. On Breastcancer.org, if you inquire about yoga and breast cancer you will see a very nice review of the ASCO study, which suggests that gentle yoga may ease fatigue problems, improving sleep quality in cancer survivors.

Can you tell me anything about the new drug everolimus?

Question from AngieInCO: Can you tell me anything about the new drug everolimus?
Answers - Andrew D. Seidman, M.D. Everolimus and temsirolimus (brand name: Torisel) are agents in a new class of drugs known as mTOR inhibitors. mTor is a molecule that is part of the cell's wiring to transmit signals and allow cancer cells to proliferate and behave badly. Everolimus is an agent that blocks this signaling pathway and is currently in Phase II and III clinical trials for metastatic breast cancer. It has already been approved for use in other types of cancer.

Any news for those of us who are hormone-receptor- and HER2-positive?

Question from Christine: Any news for those of us who are hormone- and HER2-positive?
Answers - Andrew D. Seidman, M.D. Currently, there are two targeted therapies that have been shown to be effective in HER2-positive metastatic breast cancer: trastuzumab (brand name: Herceptin) and lapatinib (brand name: Tykerb). These agents are either given with chemotherapy, alone, or in combination with each other. There are many new agents that are emerging to target the HER2 pathway. At this ASCO meeting, we heard about a novel combination of two drugs, both being developed by Genentech. The combination of pertuzumab (brand name: Omnitarg) plus TDM-1 was shown to have significant anti-cancer activity among women with HER2 positive metastatic breast cancer that had progressed despite prior Herceptin and prior Tykerb. Pertuzumab is a monoclonal antibody that acts somewhat differently than Herceptin. TDM-1 is an antibody linked to a chemotherapy drug, a so-called immunoconjugate. One other promising class in development for HER2-positive metastatic breast cancer is called HSP-90 inhibitors. There are many reasons for patients to be optimistic that we will make real progress in the treatment of HER2-positive breast cancer in the near future.

Are taxanes as effective in basal-like breast cancers?

Question from ElvaM: Can you elaborate on what I thought I read about the taxane drugs not being as effective or finding that they are not effective in treating basal-like breast cancer? And is that referring to triple-negative? Could you specify which taxane drugs this refers to, please?
Answers - Andrew D. Seidman, M.D. I am surprised actually by the question. In fact, if there is a particular subtype of breast cancer where the contribution of taxanes such as paclitaxel (brand name: Taxol) or docetaxel (brand name: Taxotere) is not effective, it is not the triple-negative subtype, but rather the luminal A subtype. In randomized trials, taxanes appear to contribute particularly among patients with both estrogen-receptor-negative as well as triple-negative breast cancer. There are actually two important references to this statement. One is a paper published by Dr. Daniel Hayes in the New England Journal of Medicine, I believe in 2008, and the other is a separate paper by Donald Berry in JAMA in 2006, I believe. There's no reason to be pessimistic about the role of taxanes in triple-negative or basal-like breast cancers.

Updates on nanotechnology to deliver therapies?

Question from Ann: Is there any update about nanotechnology to deliver therapies in a targeted way and thus help overcome toxicity?
Answers - Andrew D. Seidman, M.D.

There is an approved chemotherapeutic agent for metastatic breast cancer known as albumin-bound nab-paclitaxel (brand name: Abraxane). This drug uses small protein particles to enhance the delivery of paclitaxel in an effort to improve effectiveness and reduce toxicity. Randomized trials have shown that this agent compares quite favorably to older taxanes Taxol and Taxotere.

Would a test for circulating tumor cells predict future metastasis?

Question from LauraT: Do you anticipate a test for circulating tumor cells in a non-metastatic setting? I had considerable residual disease (triple-negative breast cancer) after neoadjuvant chemo (tumor removed by surgery). Would a test for CTCs help in predicting metastasis or at least give us more information to determine if scans should be ordered?
Answers - Beth Baughman DuPree, M.D., F.A.C.S. Identifying circulating tumor cells (CTCs) in and of themselves at this point would have no therapeutic benefit as metastatic breast cancer is treated when it becomes identified and symptomatic. It is unknown whether CTCs would predict the recurrence of breast cancer, and generally scans looking for distant disease are not ordered routinely unless a patient has a specific set of symptoms that would warrant investigation. Although there may be trials looking at CTCs and what the presence of them may mean, currently we are not using this specific technology outside clinical trials.
Andrew D. Seidman, M.D. Unfortunately, many promising diagnostic tools are accepted as being proven to be useful ahead of the definitive data that either prove or disprove this. I currently am not convinced that measuring circulating tumor cells improves an outcome based on any and all available data.

Recommendation to switch patients on Femara from Fosamax to Zometa?

Question from LBoch: I had stage I breast cancer and was diagnosed with osteopenia. I am currently on Femara and alendronate and have maintained my bone density. I wanted to know if there are new recommendations to switch patients to zoledronic acid in light of recent studies.
Answers - Andrew D. Seidman, M.D. Alendronate (brand name: Fosamax) and zoledronate (brand name: Zometa) are both bisphosphonates that can prevent loss of bone density in women receiving aromatase inhibitors such as Femara. Zometa has been most rigorously studied for this benefit in clinical trials known as Z-Fast and Zo-Fast. Alendronate is an oral agent and Zometa is an intravenous drug. There are provocative data that suggest that Zometa may possibly also have a direct anti-tumor effect against breast cancer. We still await other confirmatory studies, however, before we can comfortably tell patients that the use of this class of drugs will prevent the recurrence of breast cancer when used in the adjuvant setting.

What is the data on the effectiveness of ACT versus CT chemotherapy?

Question from KayD: What evidence is there in the effectiveness of ACT versus CT for chemo treatment? Dr. Slamon's thoughts on shelving anthracyclines prompts this question.
Answers - Andrew D. Seidman, M.D. We have one randomized clinical trial involving 1,000 patients that compared the use of AC (Adriamycin [chemical name: doxorubicin], Cytoxan [chemical name: cyclophosphamide]) to TC (Taxotere [chemical name: docetaxel], Cytoxan). (Jones SE. Phase III Trial Comparing Doxorubicin Plus Cyclophosphamide With Docetaxel Plus Cyclophosphamide As Adjuvant Therapy for Operable Breast Cancer. Journal of Clinical Oncology, Vol 24, No 34 (December 1), 2006: pp. 5381-5387.) This trial showed a modest benefit in disease-free survival and overall survival for TC over AC. The question posed asks for comparison of ACT versus TC. On that score, we currently lack any data. While there is a movement toward trying to make Adriamycin and other anthracyclines extinct, I, and I believe a majority of my colleagues, feel strongly that this is misguided. While anthracyclines can damage the heart, their judicious use by capable clinicians results in a very favorable risk/benefit ratio. Anthracyclines remain one of the most effective classes of chemotherapy drugs against breast cancer.

What was the most promising news from this year's ASCO?

Question from Darinda: Doctors, what, for you, was the most promising news from this year's ASCO meeting?
Answers - Andrew D. Seidman, M.D. As a medical oncologist, I would say the most exciting news for me was the emergence of a novel new chemotherapy drug for metastatic breast cancer patients whose cancer progressed despite numerous prior chemotherapy regimens. The drug, known as eribulin, is a synthetic analog of halichondrin-B, which is found in sea sponges that grow in coral reefs off the Japanese coast. This drug affects microtubules, but in a manner different than taxanes and other existing chemotherapy drugs. In a large, randomized trial involving 762 patients, eribulin was more effective than "physician's choice" chemotherapy in shrinking breast cancer metastases, prolonging time-to-progression of cancer, and prolonging overall survival. The overall side effect profile of this drug was quite acceptable. However, even as a medical oncologist, I was most excited by the surgical studies addressing axillary surgery and perhaps we'll let Dr. DuPree comment on that.
Beth Baughman DuPree, M.D., F.A.C.S. Randomized clinical trials showed that performing axillary lymph node dissection in early-stage breast cancer patients whose sentinel lymph node showed no sign of cancer spread had no impact on the patient's risk of dying. Therefore, overall survival of the patients undergoing sentinel node biopsy with axillary node dissection, compared to patients with sentinel node biopsy alone was equivalent (overall 5-year survival). The 5-year recurrence of cancer within the lymph nodes was also not statistically different. Therefore, we realize that the axillary lymph node dissection may not play as significant a role in surgical management as it had once been thought. And sentinel node biopsy to stage the axilla gives us the most information with least morbidity.
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