November 2005: Hormone-Receptor-Negative Breast Cancer

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What fuels ER/PR-negative cancer?

Question from MWhite: If hormones fuel ER/PR-positive breast cancer, what is fueling ER/PR-negative breast cancer?

Answer —Kathy Miller, M.D.: That's an excellent question, and one that is the focus of intense research. We have identified several growth factors that seem commonly expressed in ER/PR-negative and HER2-negative breast cancer. The most common of these is the epidermal growth factor receptor, or EGFR. There are several drugs in clinical trial that inhibit the EGFR. What we don't know yet is whether those drugs will be effective in this type of breast cancer.

ER-negative cancer recurrence risk?

Question from JeanneD: I am very frustrated with so little information available for treatment of ER-negative tumors. From what I read, they are the most aggressive, and with my tumor a Grade III, it really scares me. I watch the fat in my diet as well as total calories. Thirty minutes of exercise a day and adequate rest at night helps my energy level. What do you feel my prognosis is for recurrence and is there treatment for the future?

Answer —Kathy Miller, M.D.: Your individual prognosis is still influenced by the number of lymph nodes involved and the size of the tumor in the breast. You understand correctly that tumors that are ER-negative have a higher rate of recurrences in the first five years after diagnosis, but the long-term prognosis is comparable with ER-positive tumors. The good news for women with ER-negative tumors is that you derive greater benefit from chemotherapy than women who have ER-positive tumors who received the same chemotherapy. The other things that you can do to decrease the risk of recurrence is to follow a healthy lifestyle, including eating a low-fat diet and exercising regularly. You're already doing those things, so you're clearly on the right track.

Reduce recurrence risk of triple-negatives?

Question from JLegree: I am hormone-receptor-negative, HER2-negative, no node involvement. It was a small tumor. I have had chemo and radiation. There appears that there is nothing more I can do (except healthy lifestyle choices) to further protect myself. It just doesn't seem like enough. What else can I do to reduce the risk of recurrence?

Answer —Kathy Miller, M.D.: Your feelings are very common for women with your type of breast cancer. With a small tumor and no node involvement, your risk of recurrence is very low. You already had all of the treatments that you need. It may seem like it's not enough, because you're not continuing on therapy for many years as is common for women with ER-positive tumors, but that doesn't mean the therapy is less effective for you. You just get to be finished with your therapy faster. The transition from active treatment to being comfortable with follow-up is often a very difficult one for patients. You can be assured that you've done everything possible.

ER-negative diagnosis, ER-positive recurrence?

Question from AAnderson: I've heard of some women having ER-negative cancer on initial diagnosis and then a recurrence that is hormone-positive. How do we know we won't benefit from tamoxifen?

Answers —Kathy Miller, M.D.: It is very unusual for an initial tumor to be ER-negative and the site of a recurrence to be ER-positive. That is so unusual, but it is more likely that one of the two ER tests was wrong, or you were given incorrect results. There have been several studies testing the impact of tamoxifen in women whose tumors are ER-negative, and it simply isn't effective.

Jennifer Armstrong, M.D.: There are some patients who initially have an ER-negative cancer and later have another mass evaluated. There is always a question as to whether this is a recurrence of the initial breast cancer or a new breast cancer. One other possibility in this scenario is that there are two separate breast cancers. Nevertheless, as Dr. Miller explained, you don't routinely recommend tamoxifen as prophylaxis against development of ER-positive cancers in women with ER-negative tumors.

Tamoxifen to prevent HR+ recurrence?

Question from AnnG: Is there any evidence to show that tamoxifen prevents the development of hormone-positive tumors at a later date in ER/PR-negative patients?

Answer —Kathy Miller, M.D.: The short answer is no. In most women who have two separate primary breast cancers, those two breast cancers have the same ER status. So in most women whose initial breast cancer was ER-negative and who do develop a second breast cancer, that second breast cancer is also ER-negative. In women with ER-negative tumors, tamoxifen doesn't seem to decrease the risk of developing a second primary cancer.

False negative ER/PR test results?

Question from LoriT: What is the percentage of false negative ER/PR test results (e.g. sample too small), and is it ok to take hormone therapy as a precaution if you received a negative ER/PR test result?

Answers —Kathy Miller, M.D.: We don't recommend tamoxifen for women whose tumors are ER-negative since it doesn't reduce the risk of recurrence or the likelihood of developing a second breast cancer. But this crucial decision is based on having accurate results from the estrogen-receptor test on your tumor. These tests can be difficult, and can sometimes give incorrect results, either falsely positive or falsely negative. The results are more reliable when done in larger laboratories or hospitals that do these tests frequently. If there is any question about the test results on your tumor, your doctor may recommend sending your tumor to another lab to have the test repeated.

Jennifer Armstrong, M.D.: We've been using the term "estrogen-positive" or "estrogen-receptor positive" synonymously with "hormone-receptor-positive." Just to clarify, tumors that are either estrogen-receptor-positive or progesterone-receptor-positive are considered hormone-receptor-positive.

Kathy Miller, M.D.: All of those [hormone-receptor-positive] tumors should be considered for treatment with tamoxifen or other anti-estrogen therapies.

Additional treatment for ER/PR-negatives?

Question from GMurray: Even though a young woman is not a candidate for either tamoxifen or Herceptin, is there any other protective drug she could go on following her treatments of mastectomy surgery, aggressive chemotherapy, and aggressive radiation?

Answers —Kathy Miller, M.D.: At this point, no. If you've completed your surgery, chemotherapy, and radiation for a tumor that is ER/PR- and HER2-negative, you have completed all your therapy. There are several drugs in clinical trial that may be options in the future if those drugs are successful.

Jennifer Armstrong, M.D.: For women who are in such a position and are interested in consideration of other strategies, I highly recommend you talk with your physician on consideration of protocols that may be investigating such agents. Among them are vaccine trials, and your doctor can help coordinate your learning more about what may be open to you. For most women, I think Dr. Miller's earlier points are very important in that it can be very helpful to understand how much you've already done, and to feel confident that you've availed yourself of every option we currently understand to be helpful.

Did ER/PR-negative cancers lose receptors?

Question from Jess: Do you feel that ER/PR-negative tumors started out with receptors and somehow lost them? If so, wouldn't that mean that estrogen played a role in the development of the cancer?

Answer —Kathy Miller, M.D.: This is an excellent question. We used to think that ER-negative tumors were just ER-positive tumors that somehow lost the estrogen receptor. That is definitely not true. With newer techniques that allow us to look at the expression of thousands of genes in breast cancer, it is very clear that ER-positive breast cancers are different in many ways from ER-negative tumors.

We now think of ER-positive and ER-negative cancers as two different diseases that need different treatments. ER-positive tumors derive the greatest benefit from anti-estrogen therapies, while ER-negative tumors derive greatest benefit from chemotherapy.

Best chemotherapies for ER/PR-negatives?

Question from Joanne: What are the best-known chemotherapies (along with Herceptin with accompanied HER2/neu gene present) to fight ER/PR-negative breast tumors? Thank you.

Answers —Kathy Miller, M.D.: For women who have just been diagnosed and who don't have metastatic breast cancer, Herceptin has been combined with either Taxol or Taxotere, alone or with another chemotherapy drug called carboplatin.

We know from those recent trials that adding Herceptin to the chemotherapy dramatically reduces the risk of recurrence in women with HER2-positive breast cancer. That was true regardless of whether those HER2-positive tumors were ER-positive or ER-negative. We have not yet compared the different Herceptin regimens to know if there is a best choice.

Jennifer Armstrong, M.D.: There is also a lot of new information on the use of Herceptin with the regimen known as AC+T. AC+T is a regimen that combines Adriamycin (chemical name: doxorubicin) with cyclophosphamide (brand name: Cytoxan), with or without Taxol (chemical name: paclitaxel) or Taxotere (chemical name: docetaxol). There are recent reports of several large trials that now include almost 10,000 women worldwide that show the safety and efficacy of Herceptin in combination with this regimen in the adjuvant setting. (Women in these trials that were considered for AC+T with Herceptin had involved lymph nodes or large tumors or hormone-receptor-negative tumors that were larger than 1 cm.)

As Dr. Miller said, there are no trials yet comparing the different regimens with Herceptin to each other.

Recurrence and oral contraceptives?

Question from IlkeG: Why would someone with HR-negative breast cancer need to worry about not taking birth control? It would seem it doesn't apply. I'm confused.

Answer —Kathy Miller, M.D.: For many women who continue to have regular menstrual periods after their treatment for breast cancer, having an effective means of contraception is very important. With modern oral contraceptives, the doses of estrogen are very low and are less than pre-menopausal ovaries make naturally. There should be no concern about an increased risk of recurrence or new breast cancers with current contraceptives, including oral contraceptive pills. That is especially true for women whose initial breast cancer was ER-negative.

Extra chemotherapy or radiation?

Question from Dragons: I am triple negative and have nine lymph nodes affected with 2 cm sized tumors. I have finished chemotherapy and am near the end of radiation treatment. I am post-menopausal at 65 years old. Is there such a thing as extra chemo or radiation therapy? Should recurrence happen, what are the treatment possibilities then?

Answer —Jennifer Armstrong, M.D.: It sounds like you've been through a lot. There are no data that suggest that extra chemotherapy or radiation therapy has overall benefit over the risks. Because of that, when you complete this therapy you will have completed your adjuvant therapy. Should recurrence happen, there absolutely are possibilities for treatment. Hopefully that will not be the situation. Should that circumstance arise, there are sometimes surgical and always further chemotherapeutic options.

Dietary recommendations for ER/PR-negatives?

Question from KBlachley: Are there any special dietary recommendations for someone with this type of cancer to follow, with particular attention to the use of soy and any other nutritional supplements?

Answers —Kathy Miller, M.D.: You ask an important question, and one that we have new information to guide our recommendations. We have recently got the first results of the Women's Intervention Nutrition Study (the WINS study). That study randomized women who had completed chemotherapy to a nutrition intervention aimed at encouraging them to follow a diet lower in saturated fats and higher in whole grains, fruits, and vegetables, or to a standard follow-up alone.

What we learned is that the women who followed the low-fat diet had a lower risk of recurrence of their breast cancer. This diet was not based on specific supplements or eating or avoiding specific foods; it was based on shifting the balance to making healthier choices more regularly. This is one thing that we all can control, even though it can be difficult, especially around the holidays. Overall this is a very healthy diet that should also decrease the risk of heart disease and other long-term health problems, and we now know it reduces the risk of recurrence of breast cancers as well.

I will give you two separate answers depending on what type of soy you are asking about. Soy food products—tofu or soy milk—have very few plant estrogens and the plant estrogens have very little, if any, effect in the body. For most women, it is virtually impossible to eat enough soy foods to have any impact. However, I do worry about soybean supplements or extracts that you might buy in a healthfood store. Those are not regulated, and there is no way to know how much of the plant estrogens those products might contain.

Jennifer Armstrong, M.D.: I think that's a great distinction, and a very important one that's often under-recognized.

Reducing risk of metastases?

Question from Anders: Do you recommend taking drugs such as Fosamax to reduce the risk of bone and liver mets for ER-negative cancer?

Answer —Kathy Miller, M.D.: The short and truthful answer to this question right now is that we don't know. There have been three small studies looking at whether adding a medicine like Fosamax to chemotherapy and other breast cancer treatments decreases the risk of recurrence. None of those studies used Fosamax itself. They used a drug called clodronate that is similar to Fosamax.

One of those three studies found no difference in recurrence, one found a decrease in the risk of recurrence in bone mets only, and one found an increase in the risk of recurrence. A much larger study to really answer this question has been completed, but we don't yet have the results. So at this point, I couldn't recommend taking Fosamax or a medicine like it to reduce the risk of recurrence, but it is important to realize the risk of osteoporosis, especially in women who have been treated for breast cancer and may have become menopausal earlier than nature intended. For women with bone loss or early osteoporosis, Fosamax remains a very good option.

Doctors specializing in ER/PR-negatives?

Question from JLack: How can patients find doctors/investigators who are specifically knowledgeable about treating hormone-negative breast tumors? What studies are in progress?

Answer —Kathy Miller, M.D.: I don't think you will find anyone who specifically focuses or limits their practice to ER-negative breast cancers. There are many resources available to help identify ongoing clinical trials in your area or for your type of breast cancer. Those include the National Cancer Institute's website, www.cancer.gov or their toll-free number, 1-800-4-CANCER. Your local doctor can also point you to clinical trials or specialized research centers in your area that can provide more information.

Vaccine trials for hormone-negatives?

Question from CK: Can you give us an update of any breast cancer vaccine trials? Are there any for receptor-negative, non-metastatic, or metastatic patients you can point us to? What are these trials trying to demonstrate? Thank you.

Answer —Jennifer Armstrong, M.D.: There are many vaccine trials currently in progress, and the Web site www.cancer.gov that Dr. Miller just referred to is indeed an excellent resource that can help. Many vaccines are being studied in exactly the situation of patients who have completed their adjuvant therapy. The rationale behind this is the thought that the immune system might be most potent in patients who are in a state of minimal residual disease. Other vaccine studies, however, are certainly ongoing in patients with metastatic disease. Patients whose tumors are hormone-receptor-positive or negative are often included. Some trials are trying to demonstrate safety. Some trials are trying to demonstrate that the immune system can be stimulated. Other trials are trying to demonstrate efficacy.

Long-term ER-negative survivors?

Question from Chat: Seems I run across a lot of ER-negatives looking for long-term survivors to give them hope. Is our future really worse than ER-positive? Are there long-term survivors?

Answer —Kathy Miller, M.D.: Absolutely there are long-term survivors with ER-negative tumors! The timing of recurrence between ER-negative and ER-positive tumors is the biggest difference. The risk of recurrence with ER-negative tumors is highest in the first few years after diagnosis with a much lower risk of recurrence later. In women with ER-positive tumors, the risk of recurrence is lower in those earlier years, but is more constant. Most women who develop a recurrence more than five years after an initial diagnosis of breast cancer have ER-positive breast cancers.

So whether the risk of recurrence is higher with ER-negative cancer depends on when you look. If you look at the cumulative risk of recurrence at five years, there is a higher risk of recurrence with an ER-negative tumor. But if you look at the cumulative risk of recurrence at 10 or 15 years after diagnosis, there is very little, if any, difference.

Recurrence rates for ER/PR-negatives?

Question from PatiYL: I was diagnosed one year ago with hormone-receptor-negative breast cancer (1.5 cm with negative nodes). I was pre-menopausal at the time. I had a lumpectomy and then had four rounds of chemo and radiation earlier this year. My question is, do we have new data on the recurrence rates for hormone-negative, and also don't most hormone-negative cancers happen to much younger women? Thanks.

Answers —Kathy Miller, M.D.: You're right that ER-negative tumors are more common in women who are younger at the time of diagnosis, and we don't really understand why that is.

Jennifer Armstrong, M.D.: In answer to the question as to whether we have new data on recurrence rates for ER-negative tumors, I am not aware of any. But I think this is an important issue that goes back to some of Dr. Miller's earlier words. As we learn more about hormone-negative cancers and triple-negative cancers (ER-negative, PR-negative, HER2 /neu-negative), we are starting to consider entirely different types of breast cancer patterns and diseases. With time, many of us anticipate thinking about and treating these as different diseases. (This has occurred in a different type of cancer, lymphoma, where we now recognize 31 different types of lymphoma.) We suspect there are several different types of breast cancers that we are currently just beginning to differentiate.

It will take time for us to not only understand these better, and to develop tailored treatment strategies, and then even longer to recognize the impact on recurrence rates in these different tumor types. In the interim, we use a combination of features of a patient's tumor to guide treatment which Dr. Miller alluded to earlier. These include hormone-receptor status, HER2 /neu overexpression, tumor size, and lymph node status.

Goserelin used with ER/PR-negatives?

Question from Jaclin: I would like to know if goserelin is common to use in hormone-receptor-negative breast cancer?

Answer —Kathy Miller, M.D.: Goserelin (brand name: Zoladex) works by stopping the ovaries from producing estrogen, so it has only been effective in women with hormone-receptor-positive cancers.

News on metaplastic breast cancer?

Question from Cyna: Metaplastic breast cancer is "typically" triple negative. Do you know of any research or news about metaplastic breast cancer? Is there any research being conducted?

Answer —Kathy Miller, M.D.: Metaplastic breast cancer is a rare type of breast cancer that is very different from the typical ductal or lobular breast cancer. Metaplastic breast cancers start in cells that provide the supporting structure for the glandular breast tissue. Since the cells that give rise to metaplastic breast cancer are not part of the normal breast gland, they are always ER- and PR-negative. Because metaplastic breast cancers are relatively rare (less than 1% of all breast cancers), there have been very few studies limited to that type of breast cancer. We do know that they respond to chemotherapy, but we have not been able to compare different treatment options for this rare tumor.

Recent gains for triple-negatives?

Question from Jams: Today my sister has been told her cancer is back. She finished chemo and radiation just a year ago. She is hormone-receptor-negative and also HER2-negative. She will have a mastectomy now, but what gains have been made to help someone who is in her position?

Answer —Jennifer Armstrong, M.D.: A lot of gains have been made, and as your sister faces this news, it's important for her to understand that. From what you tell me, it sounds like she may have a local recurrence, in which case mastectomy remains an excellent option. Depending on what chemotherapy she just completed, she will probably be discussing with her physician whether there is going to be consideration for further chemotherapy at this time. She obviously has a sister who is watching her back, and that's a huge asset as well.

Test for ER/PR status?

Question from PYoung: Please clarify what test reveals whether one is hormone-receptor-negative. I didn't find it (or didn't recognize it) on the pathology report following my breast cancer biopsy.

Answer —Jennifer Armstrong, M.D.: The hormone receptor testing needs to be specifically requested. Usually this is done routinely by the surgeon. When patients have biopsies (usually before definitive surgery), oftentimes the sample is either small, or it is thought that hormone-receptor testing can be done on the definitive surgical specimen. So long as there is adequate tissue (which is usually the case), hormone receptor status can be requested even after the fact.

You might want to look at Breastcancer.org's section on Your Pathology Report, which will show you where to look for the information you need.

Tests after treatment for ER/PR-negatives?

Question from Laurie B: What kind of standard tests do you recommend when treatment is finished for ER/PR-negative, i.e. tumor marker, scans, or blood tests, and how often?

Answers —Kathy Miller, M.D.: There are many tests that women may have, including X-rays, CT-scans, bone scans, or blood tests. Most of those tests are not very effective in identifying a recurrence of breast cancer in women who have no symptoms or signs of recurrence on physical examination. For that reason, a regular schedule of testing is specifically not recommended. We would only recommend that those tests be done to evaluate symptoms or new physical changes. The one test that is important in your follow-up is regular breast imaging, such as mammography, on any remaining breast tissue.

Jennifer Armstrong, M.D.: As Dr. Miller just said, since the most important thing is signs or symptoms, surveillance is recommended with your health care provider and includes physical exam. I often see my patients every three months for the first year and less frequently over the next several years, but continue annual visits indefinitely.

Kathy Miller, M.D.: Many of my patients find what we call the "Two-Week Rule" very helpful. It is very common to be worried about recurrence after you've been diagnosed with breast cancer. Often, minor illnesses that you've had many times in the past take on new meaning and bring these fears back to the forefront. Having had breast cancer doesn't protect you from getting a cold or the flu or muscle aches after moving the furniture. But if symptoms don't get better the way they always have in the past or the way you think they should over a two-to-three week period, that's something that your doctor should hear about and may prompt further evaluation.

Arimidex for ER/PR-negatives?

Question from Margaret: I was recently diagnosed with DCIS, estrogen- and progesterone-negative. As I am post-menopausal, my doctor has put me on Arimidex. Is that the latest protocol? I'm a bit concerned because I've been told I'm in early osteoporosis. Should I be concerned?

Answer —Kathy Miller, M.D.: Any time you're concerned about your doctor's recommendation is a good time to ask more questions and consider seeking a second opinion. You're right to be concerned about osteoporosis and increased bone loss that may come with Arimidex. With an estrogen-negative and progesterone-negative tumor, the benefit of taking Arimidex is probably very small, if any.

Pregnancy and ductal cancer?

Question from Lisa: After a pregnancy, I developed ductal cancer. In your opinion, what should my current and future treatment plan be? Do you think I'm safe to get pregnant again? Could increased prolactin levels have caused my ductal cancer?

Answer —Kathy Miller, M.D.: It's impossible to give you specific recommendations about your treatment without knowing all of the details of your breast cancer, your previous therapies, and any other health problems you might have. We do know that very high levels of prolactin may increase breast cancers in mice, but we have never been able to find an increased risk of breast cancer associated with prolactin in women.

Deciding whether or not to become pregnant after a diagnosis of breast cancer is always difficult. There is no good suggestion that getting pregnant would increase the risk of recurrence, but based on the features of their tumors, many women may avoid or delay pregnancy because of their risk of having children that they might not be able to raise. This is clearly a difficult and individual decision, and one that will involve long discussions with both your doctor and your partner and family.

What counts as ER/PR-positive?

Question from Myra: What percentage of cells must be positive for you to consider the breast cancer to be hormone-receptor-positive? My breast cancer was only 7% ER-positive, but was 61% PR-positive, so I am taking tamoxifen.

Answer —Jennifer Armstrong, M.D.: Most people and most laboratories use a cutoff of 5-10% expression for positivity. As was mentioned earlier, expression of either progesterone or estrogen receptors is considered hormone-receptor-positive.

Why less research on ER/PR-negatives?

Question from Steph: Why is there less research out there about hormone-receptor-negative breast cancer?

Answers —Jennifer Armstrong, M.D.: Simply because it's less common.

Kathy Miller, M.D.: I'm not sure there's less research about hormone-receptor-negative cancer, but you have to remember that we can't design a therapy to target a negative, or something that is missing in the cancer. So much of the research has focused on trying to identify what does drive the growth of those hormone-receptor-negative cancers, and then developing a therapy to target those factors. That research is just now developing into therapies that are in clinical trials.

Test for epidermal growth factor?

Question from Nancy: Can a woman be tested for the epidermal growth factor?

Answer —Kathy Miller, M.D.: Yes and no. There are several tests for the epidermal growth factor, and those different tests can give very different results on the same tumor. Because these tests are newer and not standardized, the results are often inconsistent and it is not yet known which test best predicts the risk of recurrence or the potential benefits from therapies that block this growth factor. So the short answer is yes, it can be tested, but we don't know what the results mean.

Where does cancer recur?

Question from Katrina208: I had no lymph node involvement. When you say the risk of recurrence is higher in the first five years after diagnosis, where does the cancer typically recur?

Answers —Kathy Miller, M.D.: The most common sites of recurrence of breast cancer are the bones, the lungs, and liver. That's true regardless of whether the cancer involves the lymph nodes or not, although the risk of recurrence is higher in patients with lymph node involvement.

Jennifer Armstrong, M.D.: The breast is the other common site for recurrence.

No ovary removal for triple-negatives?

Question from Speed: If I am ER/PR-negative and HER2-negative, can I assume that I would not benefit from getting my ovaries removed (i.e. reduce the risk of a recurrence) as my tumor did not rely on estrogen to grow?

Answer —Kathy Miller, M.D.: You understand that perfectly. Because your tumor was ER-negative and progesterone-receptor-negative, any therapy that works by decreasing the production of estrogen or blocking the effects of estrogen in the body would not be expected to impact your breast cancer.

Chemotherapy for triple-negatives?

Question from Lana: How aggressive should the chemo be for triple negatives? I got differing opinions: one said AC x 4 followed by radiation; another said AC x 4, Taxol x 4, all dose dense, followed by radiation.

Answers —Kathy Miller, M.D.: The decision about chemotherapy starts with an assessment of the risk of recurrence if you had no chemotherapy at all. That risk of recurrence is influenced by your tumor being ER-negative, progesterone-receptor-negative, and HER2-negative. But the risk of recurrence is also influenced by whether or not the lymph nodes were involved, the size of the tumor, and the tumor grade. So a small tumor that does not have lymph node involvement may receive less aggressive chemotherapy than a larger tumor that involves several lymph nodes, even if the receptor status of those tumors is identical.

Oncologists may also give you different recommendations based on their personal philosophy and experience. In other words, they may have a different threshold of risk that may trigger them to recommend more aggressive therapy. I think it's important not just to ask your oncologist what he or she recommends, but to ask why that treatment plan was recommended. That will not only help you understand your treatment better, but it will help you know if your philosophy and thoughts about risk of recurrence and benefits of therapy match those of your oncologist.

Jennifer Armstrong, M.D.: I think Dr. Miller just raised some really key points. The original question mentioned getting a second opinion. Sometimes it can be helpful to consider a second opinion with your first doctor. What I mean by that is coming back to your first doctor for a whole new visit to discuss issues you're still grappling with, and that's a perfect time to have a second conversation where you ask what Dr. Miller just suggested—why your doctor is making those particular recommendations. As Dr. Miller mentioned, most treatment discussions are based on a risk/benefit ratio, and that ratio can be impacted by many factors and need to be interpreted in the spectrum of the patient's vision as well.

I have heard a recurrent theme throughout these questions. Patients with hormone-receptor-negative tumors are wishing they could do more. While this sentiment is not unique to patients with hormone-receptor-negative tumors, it is particularly salient. I think a lot of the discussion tonight has talked about all that is available to patients with hormone-receptor-negative breast cancer, be that surgery, radiation, chemotherapy, and lifestyle modifications including exercise, low-fat diet, and alcohol moderation.

We are discovering new avenues, new agents, coming to new understandings that are translating into new treatment strategies so quickly that it's at the same time exciting and can certainly be confusing. And that's where we get together and talk.