Breast Cancer Treatments. Joseph Crowe, MD & G. Thomas Budd, MD. Oct. 29, 2002.

Last Editorial Review: 10/23/2003

What new breast cancer treatments are being explored and developed, and how soon will these treatments be available?

WebMD Live Events Transcript

The opinions expressed in this transcript are those of the guest and have not been reviewed by a WebMD physician. If you have questions about your health, you should consult your personal physician. This event is meant for informational purposes only.

Moderator: Welcome to WebMD University. Our guests today are Joseph Crowe, MD, and G. Thomas Budd, MD, from The Cleveland Clinic.

Member: What is felt to be the most optimum margin width for a pure tubular carcinoma that will be closely followed after lumpectomy without radiation? If margins are negative, does it confer any added level of safety to have 10 mm vs. 5 mm margins? If cosmesis is not a concern, is more always better? Has anyone at Cleveland Clinic used observation alone after lumpectomy with pure tubular carcinoma?

Crowe: The question involves margins for a particular type of breast cancer called tubular breast cancer. Tubular breast cancer is a very favorable breast cancer subtype; it has a good long-term prognosis.

Given its particular classification of tubular there are many people who wonder whether it can be treated differently than a more typical type of breast cancer. Breast cancer, generally, is treated by lumpectomy and radiation therapy and the question is whether radiation therapy would be necessary and whether wide margin is more favorable.

Generally, we recommend the widest possible margin. One centimeter would be considered a wide margin. And most of the time we do use radiation therapy. However, in some situations, given the favorable nature of tubular cancer some of our patients choose not to have radiation therapy.

Member: Dr. Crowe, as one of your sentinel node patients, how are the results of the clinical trials turning out with regard to recurrence?

Crowe: Let me briefly explain the approach of sentinel node biopsy. First, it is important to understand that whether breast cancer has spread to the lymph nodes is an important indicator of whether the breast cancer will return. We call that a prognastic factor. So lymph nodes are an important prognastic factor for breast cancer. The only way to know whether breast cancer has spread to lymph nodes is to remove the lymph nodes surgically and test them -- analyze them microscopically.

The problem with lymph node removal, while it is not as common as it had once been, is arm swelling or arm lymphedema. If it were possible to identify the first one or two lymph nodes that breast cancer would spread to and if those lymph nodes could be tested and if they were negative (no cancer present in the lymph node) then the hope would be that there would not be breast cancer in any other of the lymph nodes.

Those first lymph nodes are termed the sentinel lymph nodes. There are techniques that we use during surgery to identify those sentinel lymph nodes and they're used routinely today, and the results of the studies to date have been very encouraging. So we have continued to use sentinel lymph node as part of our breast cancer staging.

However, two national trials are still being conducted to evaluate the long-term accuracy and reliability of sentinel lymph node biopsy and the results are not yet available. So it would not be considered exclusively used as a standard approach. So it is still under study but very encouraging results are coming in.

Member: What are Dr. Crowe's thoughts regarding hyperthermia treatment alone to reduce breast lesions before undergoing lumpectomy and to change from mastectomy to lumpectomy by ridding breast of one of two lesions? Also, what are his thoughts re Dr. Suzanne Klimberg's [University of Arkansas] studies about radioablation of the cancer and lumpectomy -- a day and a half procedure that leaves healthy tissues in the breast alone and avoids the problem of scarring and redness and its complications from radiation.

Crowe: These questions involve a new field of breast cancer research, which is oriented towards treating breast cancer before it is removed, or to use the word "ablating" the breast cancer without removing it. This type of an approach is very interesting and very important. However, at this point it is experimental and under investigation.

What this type of procedure involves is treating a breast cancer in some way by killing the cells that are cancer while the cancer remains in the breast. As yet, we still do not know how to determine the adequacy of this procedure and all procedures such as those in the above question need to be done in conjunction with removing the tissue after treating the cancer to ensure that the cancer has been treated completely. Clearly, this is a very important area for research during the next several years.

Member: I had a lumpectomy followed by radiation for carcinoma in situ. I had totally clean margins but am wondering if tamoxifen is the follow-up I need?

Crowe: Today it is very common to treat early breast cancer such as ductal carcinoma in situ with the approach of breast conservation. This approach involves removing the cancer with normal tissue surrounding the cancer, that is negative margins, and then adding external radiation therapy. There are two large studies published during the past several years, one from the United States, the other from Europe, that show that tamoxifen, when added to lumpectomy and radiation therapy for ductal carcinoma in situ, improves the results. That is, lowers recurrence of cancer in the breast. Therefore, we routinely recommend the addition of tamoxifen to lumpectomy radiation therapy for ductal carcinoma in situ.

Member: What new surgical treatments for breast cancer are being explored?

Crowe: There are a number of new surgical treatments for breast cancer for patients who are interested in breast conservation but who have large cancers, typically four, five, or six centimeters in size. It is sometimes possible to remove the cancer and then reconstruct the internal breast tissue, which can have a very good cosmetic result. This is termed oncoplastic breast reconstruction and involves moving normal tissue into the area that remains after the cancer is removed to create a more normal appearance. This approach is usually best for patients who have cancers in the lower portion of the breast and who have a relatively large breast size compared to the absolute size of the tumor.

For patients who require a mastectomy there are several new approaches. One approach is being developed in combination with immediate breast reconstruction and this approach involves removing the breast tissue beneath the skin of the breast but leaving as much skin as possible. And when this is performed it is called a skin-sparing mastectomy. Skin-sparing mastectomy has been used over the past several years very successfully in large centers and clearly improves the results of the mastectomy and reconstruction procedures.

In addition, however, as an extension of skin-sparing mastectomy, some centers are investigating whether leaving the skin of the nipple areola complex is feasible. This approach is called nipple-sparing mastectomy.

This approach requires complete removal of tissue underlying the nipple-areola complex and, therefore, there can be problems with the ability of the nipple-areola complex to heal or have a normal appearance because of blood supply concerns following the surgery. So this approach of nipple-sparing mastectomy is currently being developed. In our experience at the Cleveland Clinic we have excellent success with this approach performed for appropriate patients who have cancer as well as for patients who have mastectomy as part of breast cancer prevention.

Member: Anything new on the horizon for metastatic breast cancer?

Budd: There are two major thrusts in the investigation of new treatments for metastatic breast cancer. The first is the combination of currently available agents. For instance, the drug Herceptin seems to show synergistic activity against HER-2 positive tumors when combined with certain chemotherapy drugs. Current investigations are looking at new combinations of drugs with Herceptin as well as other combinations of currently available agents.

The second focus of research in the development of new approaches for the treatment of advanced breast cancer is the development of new drugs. These new drugs can be aimed at known targets, such as the estrogen receptor or the HER-2 oncogene. In addition, as new targets are identified, new drugs are being developed against them.

Member: My oncologist told me that the trial results from the anti-VEGF will not be favorable. So what does this mean for that class of drugs?"

Budd: The anti-VEGF treatment to which you are referring is a type of medicine called a monocronal antibody. This antibody neutralizes a factor called VEGF. VEGF is an angiogenic factor that promotes the growth of blood vessels in tumors. It is hoped that attacking VEGF will attack the blood supply of the tumor. In one trial performed in patients with advanced breast cancer the addition of the anti-VEGF antibody to a conventional chemotherapy drug does not appear to have prolonged the survival of patients with advanced breast cancer. We will hear more about the results of this study in December.

While disappointing, it might be that this approach will work better if it is used earlier in the treatment of breast cancer and other cancers. We need to await results of additional studies of this approach before passing judgment on the ultimate usefulness of anti-angiogenic therapy.

Member: Can you tell us what new treatments are being investigated for adjuvant therapy for women who have positive lymph nodes and are estrogen-receptor negative?

Budd: At present, most of the adjuvant studies in patients with node-positive, hormone-receptor negative breast cancer are investigating new combinations of chemotherapy drugs. Several trials are looking at how best to give the drug adriamycinl, while others look at how best to give the drug Taxol and Taxotere. For instance, it might be that more frequent administration of these drugs will be superior. In patients with tumors that over-express HER-2, several studies are investigating whether the addition of Herceptin to chemotherapy is useful. Studies planned for the future will investigate how best to give the drug that we now use and will investigate newer drugs in the adjuvant setting, such as Capecitabine.

Member: Can you tell us what treatments there are for adjuvant therapy for women who have negative nodes, tumors classified as high grade, and high risk of reoccurrence?

Budd: For tumors that are greater than one centimeter in size but which have not spread to lymph nodes under the arm, chemotherapy and hormone treatment can be considered. If the tumor is positive for either the estrogen receptor or the progesterone receptor, hormonal therapy with Tamoxifen or Anastrozole can be considered. Chemotherapy is also of use in tumors that have not spread to the regional lymph nodes. This is particularly the case if the hormone receptors are negative, but chemotherapy can also add to the effectiveness of hormone treatments. In general, the most active chemotherapy regimen employs the drug Adriamycin or the similar drug Epirubicin. The particular combination that is used in a particular case will depend not only upon the tumor characteristics, but also the health status of the patient who is to receive treatment.

Member: You mentioned earlier the idea of using two chemo agents simultaneously, as some drugs may have a synergistic effect. I am Taxol resistant and HER-2 negative, so what are some other combinations being explored?

Budd: There are new formulations of Taxol that are being explored, as well as new classes of drugs. For instance, a new class of chemotherapy drugs called the epothilones appear to be useful, even in some tumors that are resistant to Taxol and Taxotere. Other studies are looking at new combinations that involve Taxol or Taxotere. The combination of Taxotere and Capecitabine is superior in some ways to Taxotere given by itself.

Member: In what new clinical trials are you participating?

Budd: A number of clinical trials in breast cancer are ongoing at the Cleveland Clinic. Complete information can be obtained by calling the Cleveland Clinic Cancer Answer Line. A partial listing of current clinical trials would include the following:

  • A study of a new drug called Telik 286 in patients with advanced breast cancer.
  • A study of the combination of Doxil and Herceptin in HER-2 positive breast cancer.
  • A study of an immune treatment called CpG plus Herceptin in HER-2 positive breast cancer.
  • In addition, we are beginning to investigate preoperative chemotherapy with the drug Epirubicin administered at an accelerated pace prior to surgery.
  • Two important studies look at novel prevention strategy:
    • The first looks at a drug called Perillyl based alcohol in women who have had a prior breast cancer.
    • The second investigates a new hormonal approach in women who are risk to carry a mutation in the BRCA-1 or BRCA-2 genes, as evidenced by a strong family history of breast cancer.

The Cleveland Clinic Cancer Answer Line number is 800-862-7798.

Moderator: We are almost out of time. Doctors, do you have any final comments for us today?

Budd: Thank you for your questions and please feel free to call the Cancer Answer Line for additional information.

Crowe: Thank you for your questions. There are many topics that we did not have a chance to discuss this evening and many trials that we are involved in, in addition to those mentioned by Dr. Budd, and again, for further information I would suggest contacting the Cancer Answer Line.

Moderator: Thanks to Joseph Crowe, MD, and G. Thomas Budd, MD, from The Cleveland Clinic for joining us today. To learn more about breast cancer, be sure to explore all the breast cancer info here at WebMD, including our message boards and live chats.

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