December 2007: Updates from San Antonio 2007

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Updates on effects of aromatase inhibitors?

Question from Santa: Have we learned more on the long-term secondary effects of aromatase inhibitors?

Answer —Jennifer Griggs, M.D., M.P.H.: This was very reassuring. We heard the results of the ATAC trial which compared 5 years of tamoxifen vs. 5 years of anastrozole (brand name: Arimidex) and heard 10-year results of this study. It appears that the risk of osteoporosis in patients who do not have osteoporosis to begin with is exceedingly low. In other words, if your bones are healthy going into treatment with an aromatase inhibitor, at the end of 5 years you're very likely to maintain bone health. As you know, however, for women who already have thinning of the bones or osteoporosis, the aromatase inhibitors can make this worse. There was also a poster presentation that suggested that memory and other cognitive symptoms which some of us worry about with the aromatase inhibitors were not worse in women on the aromatase inhibitors. The cancer professionals are very aware that sexual side effects, in particular vaginal dryness, are very common on the aromatase inhibitors. There was not a great deal of this discussed at the meeting. Active research is going on to address this common and important side effect.

News on triple-negative breast cancer?

Question from Laurie B.: Is there anything new on the triple-negative front?

Answer —Jennifer Griggs, M.D., M.P.H.: So called triple-negative breast cancers are negative for estrogen receptors, progesterone receptors, and HER2. These tumors are sometimes referred to as basal-type tumors. It actually appears that not all triple-negative tumors are the same. There may be several types of triple-negative tumors, or at least 2 types. We are still in the process of defining the "personality" of these tumors. At this point, there are no specific recommendations, other than being quite aggressive with this type of cancer when selecting treatments after surgery, or before surgery in women who get chemotherapy before the primary tumor is removed. Understanding further who is at risk for this type of tumor may help us develop targeted detection strategies, and in patients with an inherited breast cancer risk, may even help us think about prevention strategies. Stay tuned!

New targeted meds for IBC?

Question from Bks: What is new for IBC? Any new targeted drugs in the works?

Answer —Jennifer Griggs, M.D., M.P.H.: It appears that survival in inflammatory breast cancer (IBC) may be improving with improvements in breast cancer chemotherapies. At the University of Michigan, we are developing a focused program on inflammatory breast cancer in order to push forward the field in this important type of breast cancer. It is that kind of concentrated effort that will lead to rapid advancements. At this point, we are not specifically choosing targeted therapies more often in this cancer, but as with the triple-negative breast cancers, we are consistently recommending that patients have the best possible multi-specialty care.

Research on anthracycline therapy?

Question from Roberta: What is the latest thinking about the use of anthracycline therapy given Dennis Slamon's research?

Answer —Jennifer Griggs, M.D., M.P.H.: We are getting smarter about how we select chemotherapy agents, not just the work of Dr. Slamon. We have longer term results of patients who were treated with a regimen that did not contain an anthracycline. There was a clinical trial with long term results presented that compared Taxotere (chemical name: docetaxel) with Cytoxan (chemical name: cyclophosphamide), compared to Adriamycin (chemical name: doxorubicin) with Cytoxan. You'll notice that the Taxotere-Cytoxan combination does not include an anthracycline. Patients who got the non-anthracycline regimen did not have a worse outcome and survival may actually have been higher in the patients who got Taxotere-Cytoxan. The work from Dr. Slamon and his group suggests that not all patients need anthracyclines, and we may be able to use characteristics of the tumor to decide who does and who does not need an anthracycline. But the medical community is not yet willing to make a flat statement against the use of anthracyclines. This class of drug, the anthracyclines, is extremely effective in treating women with metastatic breast cancer and to discard their use in earlier stage breast cancer seems premature. Nonetheless, because of the possible damaging effects to the heart of the anthracyclines, reserving the use of this type of drug for people most likely to benefit just makes sense. My guess is that within the next 2-3 years we will have a clearer idea of who is most likely to need the anthracyclines and who does not need them.

Updates on isolated tumor cells in sentinel lymph nodes?

Question from MAMHOP: Is there any further update regarding the significance of isolated tumor cells found in sentinel node biopsies?

Answer —Jennifer Griggs, M.D., M.P.H.: There were several presentations at San Antonio this year on the importance or significance of isolated tumor cells in sentinel lymph nodes. The weight of the evidence suggests that these tumor cells in the lymph nodes do not impact prognosis. Just to clarify: isolated tumor cells are very small collections of tumor cells in a lymph node. These can actually be present in more than one node, or even in several places within one node. But their tiny size classifies them as isolated tumor cells. If this is all that is present in a lymph node, the patient is most correctly considered as having negative lymph nodes. Such classification was supported at this year's San Antonio conference.

Research on ILC and survival rates?

Question from Nancy: Has there been any new research on invasive lobular cancer and the chances of long term survival?

Answer —Jennifer Griggs, M.D., M.P.H.: Lobular breast cancers, which make up about 5% of invasive breast cancers, can be hard to detect by standard mammography. The cells tend to, instead of grouping together, line up in rows which can make even physical exam of a lobular cancer difficult. Many women describe a "thickening" within the breast, and when the mammogram is negative, the diagnosis can be elusive. In terms of prognosis and chance of cure, lobular cancers appear to be quite similar in terms of risk of recurrence compared to ductal, although some large studies have suggested a slightly better prognosis. Although difficult to detect, lobular cancers are generally slower growing and more likely to contain the estrogen receptor which is associated with an improved prognosis. Lobular cancers are also nearly always HER2-negative, which again is associated with an improved prognosis. There is no evidence that hormonal therapy is less effective in lobular cancers. Because the tumors are slower growing and more likely to be ER-positive, the benefit of chemotherapy is smaller than it would be in a faster growing tumor.

Most accurate biopsy method for microcalcifications?

Question from Anna975: What is the most accurate biopsy method that can be used for a group of 10-15 microcalcifications in one area?

Answer —Jennifer Griggs, M.D., M.P.H.: Microcalcifications, which are calcium deposits within the breast, often prompt a further evaluation with a procedure such as a biopsy. There are many different types of biopsy needles, and as long as the specimen is large enough and taken from the correct place, I don't believe there is any compelling evidence to support one type of needle biopsy over another. Occasionally, a core needle biopsy is not successful in obtaining the right type of tissue or sufficient amounts of tissue. In this case, a patient may require an open procedure when an incision is made. This is called an "excisional biopsy" and is not considered treatment, but is rather considered a diagnostic procedure. I have very low levels of enthusiasm for a procedure called a "fine needle aspirate." A fine needle aspirate involves just what it sounds like, the insertion of a very small needle into the abnormal area and because it doesn't get enough tissue, should not be used to rule out a cancer. In other words, if a physician is concerned that there may be a malignancy or pre-malignancy present, a fine needle aspirate is helpful only if it indeed shows cancer. If a fine needle aspirate is negative, the patient should proceed to a more adequate biopsy such as a core needle biopsy.

Updates on Herceptin for early stage HER2+?

Question from Alyosha: Can you please comment whether there has been any update on the use of Herceptin for early stage HER2-positive breast cancer? Is there further research on the success of the clinical trial with AC + T + Herceptin that began a few years ago?

Answer —Jennifer Griggs, M.D., M.P.H.: The use of Herceptin (chemical name: trastuzumab) in early stage breast cancer has been approved by the U.S. Food and Drug Administration (FDA) because the results of the clinical trials were so compelling in improving recurrence rates from breast cancer. Herceptin is an antibody therapy that is given usually in combination or shortly after chemotherapy, that works differently from chemotherapy. In patients with breast cancer that is HER2-positive, it significantly reduces the risk of metastatic (Stage IV) disease. Worldwide data support the use of the drug in this setting. I expect that the survival benefit will continue over the next few years.

One study we're waiting for is the result of the HERA (Herceptin Adjuvant) trial, conducted in Europe. Patients on this study who got Herceptin were randomly assigned to get 1 year of the drug or 2 years of the drug. We are waiting to see if a longer period of treatment might give some women additional benefit. These results were not updated at San Antonio. A study that just started in Europe and will be starting here in the U.S. will be comparing Herceptin with lapatinib (brand name: Tykerb) in women with early stage breast cancer. Tykerb is an agent that also targets the HER pathway and the results of this trial will be critical in continuing to improve survival rates in breast cancer. Obviously, this kind of trial takes a long time to conduct and we are always grateful to the doctors and patients who participate in this kind of study.

Herceptin used more than 1 year after chemo?

Question from Bre: I was diagnosed with Stage I, grade 3 HER2 invasive ductal carcinoma before Herceptin was approved. Has anything been studied about using Herceptin 3 1/2 years after initial chemo?

Answer —Jennifer Griggs, M.D., M.P.H.: When the Herceptin study results were released for early stage disease, patients who had finished chemotherapy less than a year before were offered Herceptin. The overwhelming consensus of the medical community was that introducing Herceptin into patients who were more than a year out needed to be studied before it could be recommended. Herceptin is usually given with chemotherapy or shortly after chemotherapy is done. I'm not aware of any studies about reintroducing Herceptin in people who are further out.

Ixempra for IBC?

Question from Hania: Has the new drug Ixempra shown any promise in the treatment of advanced Stage IV inflammatory breast cancer (triple positive) HER2-overexpressing, but insensitive to Herceptin, Tykerb, and Xeloda?

Answer —Jennifer Griggs, M.D., M.P.H.: Studies focusing specifically on the use of this class of drug called the epothilones have not been done, but there's no reason to think that the drug, Ixempra (chemical name: ixabepilone), would be any less effective in inflammatory breast cancer that has progressed on other chemotherapy agents. So certainly a trial of this drug would be warranted, given its promise in clinical trials.

New medicine for bone loss?

Question from Winter: Please spell the name of a new twice-a-year drug for bone loss.

Answer —Jennifer Griggs, M.D., M.P.H.: This is denosumab. This is an antibody that targets the receptor of nuclear factor kappaB ligand (RANKL), which is involved in bone remodeling. The clinical trial presented of this drug was very promising. Ongoing research is likely to show additional uses of this drug, for example treatment of metastatic disease to bones. At this point, denosumab is not approved in this setting. Other drugs are FDA approved for preventing and treating bone loss, whether it is from chemotherapy-induced menopause, aromatase inhibitors, or osteoporosis or osteopenia not related to cancer and its treatment.

The intravenous drugs approved by the FDA offer a treatment option for people who are not able to tolerate the drugs when they are given as a pill. Many patients try to take the oral medications and develop symptoms such as pain with swallowing or severe heartburn and give up on the medications altogether. Now that we have other options, you have other choices you can talk about with your physician to maintain the health of your bones in the long term.

Another thing you can do to improve the health of your bones is to participate in weight-bearing exercise. Walking may not be enough healthy stress on the bones, and you may want to think about more vigorous activities. Examples would be short spurts of jogging, jumping rope, and weight training. Weight training is particularly effective in preserving bone health. Sufficient amounts of Vitamin D, usually in the form of supplements, and calcium are also important in maintaining bone health.

New treatments for peripheral neuropathy?

Question from Kris: Are there any new treatments for chemo-induced peripheral neuropathy?

Answer —Jennifer Griggs, M.D., M.P.H.: There are some new studies being started right now to address this important and all too frequent side effects. Stay in touch with your oncologist to see if one of these studies might be available to you.

DEXA scans, Fosomax, other meds for bone loss?

Question from Julie W.: There seems to be a lot of new info about treating bone loss in breast cancer survivors. I'm on Fosamax. In order to monitor how well it's working, should I be getting a DEXA scan annually? Should I be asking my oncologist about medications other than Fosamax?

Answer —Jennifer Griggs, M.D., M.P.H.: DEXA scans are used to measure bone mineral density and should be done more frequently in women on aromatase inhibitors than in women not on aromatase inhibitors to help decide if and when drugs such as Fosamax (chemical name: alendronate sodium) should be started. Once women are on Fosamax, close follow-up is warranted but it's not entirely clear if more frequent DEXA scans are helpful. The reason for this is there's a lot of "noise" with the test. What I mean by that is a test done even 2 days later can show changes from the first one. The tests have a certain amount of wiggle room in their interpretation. If a patient is able to take her Fosamax regularly, is taking Vitamin D and calcium, and is participating in weight bearing exercise, we would expect to see stabilization of her bone health. In a woman with very severe osteoporosis more frequent follow-up is probably warranted. There are other drugs that can be added to Fosamax, such as the inhaled Miacalcin (chemical name: nasal calcitonin), but the added benefit of this drug over Fosamax is difficult to estimate.

In summary, talking with your doctor about the best frequency of DEXA scanning in your case makes sense because the recommendations will vary depending on how severe your osteopenia or osteoporosis is. New guidelines for monitoring and treating the bones are being developed now by the American Society of Clinical Oncology (ASCO). When these come out, we may have some more clarity around optimal monitoring of bone health.

News on Arimidex and radiation?

Question from Marcia: Do you have any information on taking Arimidex while on radiation?

Answer —Jennifer Griggs, M.D., M.P.H.: The timing of radiation therapy and hormonal therapy is sometimes highly debated among breast cancer providers. Without a lot of data to support either approach, some doctors start aromatase inhibitors independent of the radiation schedule; in other words, they pay no attention to when radiation is given and start the drug when chemotherapy is done or at the time of initial consultation. Other providers wait until radiation therapy is done.

I suppose that there is a theoretical reason to wait in starting any hormonal therapy until someone is done radiation. The reason would be that radiation works on cells that are dividing, and hormonal therapies slow down division of cancer cells and could theoretically reduce the effectiveness of radiation. In the case of tamoxifen, another hormonal therapy, there does not appear to be any downside of starting tamoxifen along with radiation therapy or in the middle of radiation therapy.

In terms of risk of recurrence, starting tamoxifen before radiation was done was not shown to increase recurrence rates. We don't have a similar trial with the aromatase inhibitors, so many doctors just pick an approach and stick with that for their patients.

My feeling is that a patient who has many symptoms as she recovers from surgery and chemotherapy and is facing radiation therapy is probably well served by giving her only one treatment at a time. That is, I let her recover from chemotherapy and her surgery, start radiation, and then add a new drug. In a woman who had just surgery, no chemotherapy, is feeling well, and starts radiation therapy, starting her aromatase inhibitor at the beginning or in the middle is not likely to affect her tolerance of radiation or her long term outcome.

On the other hand, if the radiation therapy doctor who is taking care of the patient has a strong preference to wait until the end of radiation, I'd certainly offer no objection. We work as a team, and respecting the other doctor's opinion is very important. Most radiation lasts 6 ½ to 7 weeks, and holding off on aromatase inhibitors for that length of time is not likely to put the patient at a higher risk of recurrence.

In summary, what your doctors recommend is based on their experience and their preferences, tailored to your individual situation.

Chemo or radiation for all tumors?

Question from Jennifer: Is it still the opinion of many that small, early breast tumors do not get chemo or radiation, or is it now going towards ALL breast cancer patients be given some type of chemotherapy or radiation?

Answer —Jennifer Griggs, M.D., M.P.H.: Breast cancer is treated with several different types of treatment, as you know. Although the stage of the cancer, that is, the size of the tumor and the involvement of lymph nodes, is very important in helping us decide treatment, also important is the biology or "personality" of the cancer. We might be more aggressive in treating an 8 mm cancer than we would be in treating a 2 cm cancer. What I mean by that is if the 8 mm cancer has very busy cells with a high grade and is negative for the estrogen receptor and positive for HER2, I would be more inclined to offer that patient chemotherapy than I would be somebody with a slow-growing 2 cm tumor that is ER-positive and negative for HER2.

We have additional help in making tumor therapy decisions in some patients with a technology called genomic profiling. This is a test done on the primary tumor and does not require any additional surgery or bloodwork. The tumor is sent for tests that further define the tumor's personality. There are several brand names for this test. The one used most often at this point in the U.S. is OncotypeDX. This test, again done on the breast cancer tumor already removed, returns a risk of recurrence score, and further defines the tumor's likelihood to come back elsewhere in the body. The test right now is only used in patients who have negative lymph nodes and whose cancer is positive for the estrogen receptor. If the patient has a tumor that does not fit those two criteria, the Oncotype test or other genomic assays cannot at this point be said to be helpful. The decision about radiation therapy depends on the patient's tumor size, the type of surgery she has, and the lymph node involvement.

For most women who have a lumpectomy (also called breast conserving surgery), radiation after surgery is considered standard of care. Omission of radiation therapy is associated with a higher risk of recurrence in the breast and surrounding lymph nodes. There are some women for whom radiation therapy can probably be safely omitted. Women who are 70 years old or over, who have small tumors with a slower growing personality, and who had a good surgery with nice wide margins tend to gain less from radiation than other women. And a woman may decide after consultation to reserve radiation therapy for the future if she indeed has a recurrence in the breast.

To answer your question, yes, women with small tumors very often are offered chemotherapy and radiation therapy, again depending on many of the factors I discussed above.

One interesting study that came out of San Antonio this year was a study looking at women who had a small number of lymph nodes involved (1-3 involved) who had tumors positive for the estrogen receptor. In 2 studies, the genomic profiling technology that I described above was shown to help predict which patients would have recurrent breast cancer. While we're certainly not going to start at this point using the genomic profiling assays to decide who does and who does not get chemotherapy with 1-3 positive nodes, additional studies that show the same thing will undoubtedly expand indications for this assay or test. But none of us is willing to not give chemotherapy to women with positive nodes on the basis of this test alone.

New developments for metastatic treatment?

Question from Wally: Were there any new developments discussed that offer hope to curing Stage IV metastatic breast cancer?

Answer —Jennifer Griggs, M.D., M.P.H.: Stage IV cancer, which refers to cancer that has spread to other parts of the body, is generally viewed as a chronic disease. What I mean by that is the patient will be dealing with her breast cancer for the rest of her life. Some people liken this to diabetes or other chronic problems like hypertension. I think cancer is different, and many of my patients don't appreciate that analogy. Nonetheless, I think it's worth preparing you for that sort of comment.

Some women with Stage IV breast cancer can live many months or even years without any evidence that their cancer is still present in their bodies. For most women, however, they will be on some form of treatment, occasionally with breaks from treatment, indefinitely. This is not to say we aren't trying to cure Stage IV disease. All of us would like nothing more than to be able to tell patients with metastatic disease that we have a cure. We would all like to be put out of business!

In the meantime, while we wait for the dramatic advances we all hope are coming, what I can tell you is that survival in Stage IV disease has improved substantially due to new drugs, better drugs, and better tolerated drugs. Please don't give up hope that the advances we are seeing in improving cure rates in early stage disease might not also improve outcome in Stage IV disease.

Hope for a breast cancer vaccine?

Question from Terry: I saw a Discovery Health Channel show a year ago where a woman neurosurgeon was removing brain tumors and her husband, a neuroscientist, was creating a vaccine from the tumor cells and injecting this back into the patient to prevent redevelopment. I think it was probably a experimental program and they were both at UCLA. Is anything like this in the works for breast cancer?

Answer —Jennifer Griggs, M.D., M.P.H.: Vaccines for breast cancer have intrigued scientists and patients alike for decades. At this point, vaccines seem to be able to evoke an antibody in the patient; in other words, the patient is given the tumor and they develop antibodies to the tumor in some cases. At this point, however, we don't have any studies showing that this translates into a response to treatment. So an effective vaccine can be effective in getting a body to respond by creating antibodies, but we have yet to see this translate into anti-cancer activity of those antibodies. This is a very hot area of research, however, and if we get smarter in understanding breast cancer biologies, I wouldn't rule out an effective vaccine offhand.

Ovary removal and BRCA gene?

Question from Northern CA: Can you comment about being diagnosed with the BRCA gene and the need to have the ovaries removed?

Answer —Jennifer Griggs, M.D., M.P.H.: BRCA genes refer to genes that we inherit from our mother or father that increase our risk of getting breast cancer over our lifetime. At this point, there are 2 BRCA genes, called BRCA I and BRCA II. The genes are a little different in the risk they give in developing breast cancer. Women with BRCA I or BRCA II mutations are at higher risk of developing ovarian cancer as well. A woman should consider BRCA testing if she has been affected by breast cancer at an age of less than 40 years, or if she has multiple affected first degree family members or second degree family members, a family history of ovarian cancer, a family history of male breast cancer, or if she has had breast cancer and is of Ashkenazi Jewish descent. breastcancer.org has a wealth of information about who should consider testing for the BRCA genes.

If a woman is found to have a BRCA gene, either BRCA I or BRCA II, and has had breast cancer, she may want to consider removal of the ovaries and fallopian tubes to reduce her risk of getting ovarian cancer or a cancer in the fallopian tubes, which can also happen. If she has had breast cancer and continues to have functioning ovaries, removing the ovaries may also reduce her risk by lowering estrogen, reduce her risk of getting breast cancer again.

For a woman who has a BRCA I or BRCA II mutation but has not had breast cancer, her major concern will be avoiding getting breast cancer or ovarian cancer; in other words, preventing these cancers. Knowing that she is at high risk of getting breast cancer, the patient and her doctors may consider breast surgery, that is removal of the breasts, and/or removal of the ovaries. In a premenopausal woman, removal of the ovaries will lower her estrogen levels and may lower her risk of getting breast cancer. In other words, by having her ovaries out, she may reduce her risk of both ovarian cancer and breast cancer. If she is postmenopausal, removing the ovaries will most likely not reduce her risk of breast cancer, but may reduce her risk of ovarian cancer.

In women who have BRCA I or BRCA II gene mutations, MRI of the breast is often offered as an additional form of screening (if she has never had breast cancer) or follow-up, if she has had breast cancer. Discussing these options with your physician is appropriate as soon as you find out you have one of these mutations, so that you can plan your future prevention strategies.

Stem cell research and breast cancer cure?

Question from Diane: Are you getting more info about stem cell research? My doctor said this is where the cure for cancer will be found.

Answer —Jennifer Griggs, M.D., M.P.H.: Great question. Stem cells or stem-like cells refer to cancer cells that give rise to all subsequent cancer cells. They're like the prototype or matriarch, if you like, although I tend to dislike the idea of cancer cells as having a feminine personality! There is some suggestion that cancer stem-like cells may not respond to other treatments that we use to treat the subsequent cancer cells that we can actually see. In other words, the stem cells are resistant to our typical chemotherapy drugs. The chemotherapy drugs that we use in daily practice only treat the offspring of the leader of the clan. This stem cell is sitting there, continuing to live in the face of these chemotherapy drugs. So that describes the concept of the cancer stem cell. Currently, a great deal of research is being done on developing drugs that target the stem cell or stem-like cell, and I am optimistic that we will have data about these therapies in future San Antonio conferences as the enthusiasm for this approach is very high. All that being said, not all scientists have bought into the idea that there is such a thing as a cancer stem cell. I hear your doctor's conviction that we need to do something different for cancers that appear particularly difficult to treat, but, and this is a tired song, the proof is in the pudding and we need clinical trials to prove that the concept is correct.

Small tumors to be treated with chemo?

Question from Schaberg: The New York Times posted a story about the aggressiveness of some small tumors that was presented in San Antonio. This has really frightened me. I had a .3 mm ductal carcinoma (ER/PR-negative; HER2/neu-positive; negative lymph nodes) and was treated with surgery and 6 weeks of radiation, but no chemo. Has that treatment protocol now been shown to be inadequate? If so, what do we do?

Answer —Jennifer Griggs, M.D., M.P.H.: A tumor as small as yours is rarely treated with chemotherapy. Very few women have tumors that small, and very few women with such small tumors are included in clinical trials, so it's hard for us to know what the benefit is of treatment such as chemotherapy and Herceptin in your case. Many women with a tumor that is so small are also found to have non-invasive breast cancer (ductal carcinoma in situ) which is often picked up on a mammogram. According to current guidelines developed by experts who take into account literature and studies from around the world, chemotherapy in your case would rarely be offered. Even in the studies showing that small tumors can be associated with a poor outcome, that is usually associated with tumors larger than the one you had; for example, 6 mm or 8 mm or 1.5 cm tumors. So you were treated according to our best evidence that we have at this point.

Link between insulin and breast cancer?

Question from EllenA: Please comment on Dr. Pollak's hypothesis that there may be a relationship between insulin and IGF-1 levels and breast cancer. Could insulin resistance increase risk? Are there oncologists who specialize in endocrinology? Thank you for any suggestions.

Answer —Jennifer Griggs, M.D., M.P.H.: The work presented at San Antonio builds on a large body of work, suggesting a connection between insulin growth factors and breast cancer. We have long known that high insulin levels, for example those seen in heavier women, are associated with a higher risk of breast cancer. (Not all studies have shown this to be the case.) But the connection between insulin growth factor and breast cancer development and progression is being studied primarily by oncologists and endocrinologists together in addition to our laboratory colleagues, that is scientists who don't treat patients. Many breast oncologists view themselves as endocrinologists of sorts, because we deal with cancers that are dependent on hormones in many cases.

In addition to insulin growth factor, there are other substances that are altered in patients who have diabetes and who are heavy, and there is a tremendous amount of work being done in this area in terms of both understanding the development and growth of breast cancers and with an eye to developing therapies that could counteract the effect of insulin growth factor and other similar substances. One thing that is particularly interesting is women who undergo gastric bypass surgery have a lower risk of dying of cancer, and this excludes people with cancer. In other words, people are less likely to get cancer after bariatric surgery. It's possible that women are more likely to get mammograms after having such a procedure and that they may be diagnosed earlier because they change their relationship to their doctor after they lose a lot of weight. But equally likely is that losing a lot of weight alters metabolism of insulin, insulin growth factors, and another substance called adiponectin and other inflammatory substances. This is a very exciting area of research.

New treatments for lung mets?

Question from Ceco: Are there any new and effective ways to diagnose and treat breast cancer which has metastasized to lung tissue beyond CT scans and chemotherapy?

Answer —Jennifer Griggs, M.D., M.P.H.: When undergoing treatment for Stage IV disease with metastasis to the lungs, your whole life can revolve around doctor’s appointments, waiting for test results, changing treatments, and searching for hope.

We have targeted therapies that indicate to me that we're getting smarter in treating cancer. So women whose tumors are positive for HER2 can be offered Herceptin and Tykerb. For women whose tumors are HER2-negative, there is some evidence that targeted therapies such as Avastin (chemical name: bevacizumab) may be helpful, but again, these are combined with chemotherapy.

It sounds as though your tumor is not ER-positive. For women whose tumors are positive for the estrogen receptor or progesterone receptor, hormonal therapies can also be used. These were really our first targeted therapies in any cancer, if you think about it. For women whose tumors are responsive only to chemotherapy, at this point we are optimistic about developing additional targeted therapies and chemotherapies that are better tolerated.

In addition, there is research being done on the use of very high doses of focused radiation to metastatic lesions in the lungs, for example. Usually radiation in this setting would be appropriate if someone had only a few areas of cancer.

The energy and commitment of breast cancer researchers is overwhelming and I tell my patients with Stage IV disease not to give up hope for better and smarter treatments. With the pace of scientific discovery in this day and age, I don't think that's false hope.

New test to determine cancer spread?

Question from CindyM: The latest issue of Time magazine lists the 10 Biggest Medical Breakthroughs: #2 is "Test for Metastatic Cancer, the GeneSearch BLN Assay, which can tell doctors midsurgery whether breast cancer has spread, allowing them to remove the affected lymph nodes during a lumpectomy or mastectomy.” Does this mean there is no need for a sentinel lymph node biopsy?

Answer —Jennifer Griggs, M.D., M.P.H.: This is a test done on lymph nodes removed during the time of the breast operation. It's actually done on the sentinel lymph node, and does not eliminate the need for the sentinel lymph node biopsy. The advantage of this type of study is that it can return results more quickly than a pathologist who has to slice through the node in 100 different slices and look at them under the microscope.

This type of test looks for cancer cell genes in the lymph node tissue. The assay that you refer to is one of several types of tests that can be done on lymph nodes. Certainly if we are confident in the results of this test, this technology could reduce the need for people having to go back to the operating room to have more surgery.

Sentinel lymph nodes can tell us if the first node that the breast leads to, the lymph node draining the breast, has cancer in it. If the sentinel lymph node is positive, women are usually advised to have another surgery to remove additional nodes under the arm. This assay, the BLN assay, could avoid the need to go back to the operating room in somebody with a sentinel node that is positive, and she would have her second surgery at the same time she has her initial surgery.