Ask the expert: Q & A on therapies for breast cancer


Erica Mayer, MD, MPHErica Mayer, MD, MPH 
Harold Burstein, MD, PhDHarold Burstein, MD, PhD 

Dana-Farber Cancer Institute partnered with CancerConnect so that patients could ask Harold Burstein, MD, PhD, and Erica Mayer, MD, MPH, their questions about therapies for breast cancer. Drs. Burstein and Mayer are breast oncologists in the Center for Breast Oncology at Dana-Farber's Susan F. Smith Center for Women's Cancers. You can find patients' questions and the doctors' answers below. 

ER-positive breast cancer and nutrition

Q: I am estrogen-positive and am wondering what foods besides soy to avoid. Also, how do I deal with the age-old problem of vaginal dryness and not being able to use anything beside Replens to help. Any suggestions? 

Dr. Mayer: There are no firm data that eating soy, or other specific foods, will increase risk of cancer recurrence. In general, we recommend what many consider a healthy diet: plenty of fresh fruits and vegetables, lean meats in moderation.

As for vaginal dryness, if non-hormonal vaginal moisturizers are not adequate to control symptoms, one can try local hormone therapy in the form of estrogen suppositories or rings. Although we do try to avoid hormone exposure after a diagnosis of estrogen receptor positive breast cancer, there are no data that using local hormone therapy will increase risk of recurrence, and these agents can help quality of life if vaginal dryness symptoms are very bothersome. You can discuss your candidacy for these medicines further with your provider.

Investigative forms of vinorelbine and trastuzumab

Q: What is the possibility of the oral form of vinorelbine and the subcutaneous form of trastuzumab being approved for use in the US, as it is in Europe? What are the barriers involved in gaining such approval? 

Dr. Mayer: These agents remain under study at this time; it is not clear if or when they will be available in the US.

Faslodex

Q: My question is two-fold. I take Faslodex as my adjuvant therapy. I did not have metastatic cancer; I take it because I was unable to take any other medication due to terrible side effects or allergic reactions. What are the statistics for someone taking it for that reason? Also, I am now having terrible joint pain and inflammation, which started slowly and is progressing. I hate to take other medications on top of this one as I have a terrible history with side effects with lots of medications (not just cancer medications). Do you believe it could come from the Faslodex, and are there any other options out there for me? 

Dr. Mayer: Fulvestrant is not a typical agent used as adjuvant therapy for breast cancer, and there is no clinical trial information to describe the percentage benefit to be expected from this therapy. If you are having new symptoms, you should discuss them with your provider for further workup and treatment options.

HER2+ Stage IV breast cancer and duration of therapy with Zometa and Herceptin

Q: I was diagnosed with HER2+ breast cancer in May of 2006, After having a lumpectomy we found out there were mets to the liver and skull, so I went from Stage I to Stage IV in 2 weeks. I did several rounds of Adriamycin, Taxotere and Cytoxan, then had liver resection, started on Herceptin, Zometa, Gemzar and Carboplatin. Dropped Gemzar and Carboplatin as tumor markers weren't dropping. Then had 33 rounds of radiation. I'm still on Herceptin and Zometa. All my scans have been showing NED for 5 years now, and my tumor markers are almost normal. 

My question is: What are your opinions on staying on the Herceptin and Zometa? Sometimes I feel like I don't need to be on them any longer as I'm doing so well. But going off them scares me. 

Dr. Mayer: Congratulations on doing so well for 7 years! The benefits of long-term treatment with Zometa are not known, and there can be risks of long term toxicity; therefore you could consider either stopping that agent or reducing to twice-a-year infusions. As for Herceptin, this agent is typically continued indefinitely in patients with metastatic HER2-positive breast cancer and stable heart function. I would suggest continuing on Herceptin for the time being.

The investigative drug bazedoxifene

Q: When will bazedoxifene be available for metastatic breast cancer? I know studies are being, or have been, conducted at Duke. 

Dr. Mayer: Bazedoxifene is an osteoporosis medication which showed an anti-cancer effect against breast cancer cells in a laboratory experiment. Whether the drug would help treat breast cancer in a human is not known and needs to be studied. The effects of other osteoporosis medications on breast cancer outcomes have been variable, so it is not clear that this new drug will actually be helpful for people until a trial is done. If you are interested in new medications for breast cancer, please speak to your provider about participating in a clinical trial.

Clinical trials and BRCA1 gene mutations

Q: My question is on behalf of my sister, who has the BRCA1 gene. Her cancer returned on a lymph node, which they tried to operate and remove but was too deep and near an artery. Was given chemo to shrink, but had severe bowel problem side effects. Her second line of chemotherapy was not effective, either. Her third chemo may be working but is giving her severe planter syndrome. They have stopped chemo due to this. Considering a trial now. Have you any latest thing you can suggest, as we are at wits end? 

Dr. Mayer: This sounds like a difficult situation for your sister. If a cancer is thought to be resistant to standard chemotherapies, consideration of a trial is a reasonable option. Alternatively, she can discuss with her provider if obtaining another opinion on her care at a center that frequently treats women with BRCA1 gene mutations would be helpful.

Duration of Aromasin

Q: I have stage IV breast cancer with mets to bone, which I had partially removed. I have been on Aromasin for the last 5 years. I am worried about long term effects as I am developing neuropathy in my feet and am wondering if I can stop taking this drug. Thank you. 

Dr. Mayer: Congratulations on 5 years on Aromasin (exemestane) for Stage 4 breast cancer! As you are doing well with a diagnosis of metastatic breast cancer, in general, we would suggest continuing on the exemestane. If you are experiencing side effects, you could consider taking a month off and then restarting, as sometimes that helps "reset" the body and improves symptoms.

Triple-negative breast cancer treatment, follow up and recurrence prevention

Q: What is the standard of care after treatment for triple-negative breast cancer? Lumpectomy, chemo and radiation were completed. Should there be regular blood tests, PET scans, etc.? Is there any medication that can be given to TNBC survivors to help prevent recurrence? 

Dr. Mayer: Following completion of active treatment for any breast cancer survivor, follow-up care includes regular visits with your providers, which should include physical examination and annual mammogram if there is breast tissue. For a breast cancer survivor who is doing well and feeling well, there is no role for routine blood tests or body imaging. There are new agents being evaluated in clinical trials to try to help outcomes in people with triple negative breast cancer, and you can talk to your provider about whether such a trial is available. There are also increasing data that getting regular exercise and avoiding gaining weight may be helpful for survivors, particularly those who have had triple negative breast cancer.

Duration of treatment with Herceptin

Q: What is your medical opinion regarding the long term use of Herceptin (+6 years)? What other options are available for the over expression of Her2 over the long term? 

Dr. Mayer: For adjuvant therapy of breast cancer, Herceptin is used for one year. For a patient with metastatic disease, Herceptin is continued indefinitely, as long as cardiac function is stable. There are no other medications with enough data to support their use in place of long-term Herceptin for metastatic disease.

CYP2D6 and tamoxifen

Q: I recently finished treatment for breast cancer. I am Stage 2a Grade 2, Oncotype 17, post menopausal and did a lumpectomy and radiation, with no chemo. I am now on tamoxifen for 2 years to be followed by some AI. 

My questions: 

1. I was not tested for CYP2D6 to see if I metabolize tamoxifen. Should I be, and do some places do this routinely? 

2. If the whole idea of ER/PR-positive breast cancer is to keep the levels of estrogen down, why don't they do tests for estrogen to see if treatment is working? 

Dr. Mayer: Trials investigating the relationship between CYP2D6 and outcomes with tamoxifen have not shown consistent results; therefore, at this time CYP2D6 testing to guide decisions about tamoxifen is not recommended. The mechanism of action of tamoxifen is to block estrogen, not decrease levels, therefore checking estrogen levels will not provide a measure of the effectiveness of the agent.

Exemestane and side effects

Q: What is the association, if any, between exemestane and heart problems? Why does this appear in the list of side effects? 

Dr. Burstein: There are no dramatic risks of heart disease with exemestane. However, there can be increases in cholesterol and in blood pressure with aromatase inhibitors. Women should get their usual surveillance for those problems.

Breast Cancer and lymphoma

Q: In 2007 I had a lumpectomy for a stage I grade I invasive ductal cell carcinoma. Shortly after the surgery my blood counts, which had been normal all along, began to plummet. I saw my oncologist and two GPs, who all said not to worry, the counts "weren't that bad." However, I had to change doctors because of my health insurance, got my records from my primary care, and went to a new doc. He immediately ordered a panel of blood tests because one of my records showed a "significantly enlarged spleen," which went undiagnosed until 2011. I was told I had splenic marginal zone lymphoma. I feel as if the two surgeries unleashed the lymphoma. My question is: in your experience, does the type of BC I had lead to – or is it somehow connected to – lymphoma? 

Dr. Burstein: So far as I know, there is absolutely no relationship between breast cancer and lymphoma. My guess is that the lymphoma was found after the blood count problems as a coincidence when the blood tests were done at the time of your breast cancer diagnosis.

Liver metastasis

Q: I have struggled with breast cancer for the past 4 years. A liver met appeared in 2011; this was surgically removed a few months later. After a couple of more months 4 new mets were detected, under anastrozol therapy. Everolimus + aromasin didn't help at all; I started Xeloda, which went very well until August 2013. I am now on paclitaxel. Is surgery or radiotherapy an option to remove the liver met? 

Dr. Burstein: In general, we do not remove liver metastases from breast cancer. Drug therapy is the usual standard approach. Surgery can be associated with substantial risks, and most of the time, the cancer returns even after the surgery. Standard radiation therapy is quite toxic to the liver. There are selective ways of giving radiation that might minimize the side effects, although the same issues about the cancer popping up elsewhere can apply.

Taxol (paclitaxel)

Q: Does treatment with Taxol have added value for women with estrogen/progesterone-positive and Her2-negative tumors, such as mine. Ablation, followed by radiation, at the moment 3 (out of 4) AC chemo's to be followed by 12x Taxol and hormonal therapy. 

Dr. Burstein: AC followed by taxol is a very standard chemotherapy treatment for node-positive breast cancers, especially in younger women and especially if the cancer is higher grade.

Cardiac toxicity and breast cancer treatments

Q: From what I have read, it appears that more attention is now given to the possible heart toxicity of such medications as Herceptin, AC chemo and even the AIs. I researched these therapies back in '06 and refused them for that very reason. How are they used differently today, taking into consideration pre-existing heart issues of some patients? Does the same hold true of radiation treatments for those at risk of heart issues? What is the collateral damage and death rate from treatment? Thank you. 

Dr. Burstein: On the one hand, each of these treatments (trastuzumab, anthracycline-based chemotherapy, AIs, and radiation therapy) can cause heart damage. The actual kind of heart damage may differ. Trastuzumab (Herceptin) and AC chemo can damage the heart muscle, leading to heart failure. AIs can cause elevated cholesterol and hypertension. Radiation can cause accelerated coronary heart disease.

Fortunately, however, the risk of major (or even minor) heart problems with these treatments is very low. Each of them can be very important parts of a breast cancer treatment program. We monitor heart function carefully in patients getting trastuzumab or AC, and avoid those treatments in women with pre-existing heart problems. As a result, heart damage from these treatments is real, but rare.

Asynchronous metastasis

Q: For patients who develop asynchronous metastasis (tumor markers that differ from the primary tumor), what is the current approach to treatment? 

Dr. Burstein: The markers drive the treatment. If the cancer is likely to be estrogen receptor (ER)-positive, we offer anti-estrogen therapies. If it is HER2-positive, we offer anti-HER2 therapies.

It is sometimes hard to know which is the "real" marker profile when there are discordant results. That is a conversation to have with your clinical team.

Soy

Q: What is the present thinking on eating products that contain soy for estrogen-positive breast cancer? 

Dr. Burstein: There are absolutely no data that eating soy affects breast cancer one way or the other. The phyto-estrogens that are found in soy are not known to have any physiological effects. If you like soy, enjoy it. If you don't like soy, then don't worry about it. The various soy preparations frequently used in many foods are also not known to have any effects in breast cancer patients.

Bone health in stage IV breast cancer

Q: I have stage IV breast cancer – on zometa – does this help keep the cancer out of my bones? 

Dr. Burstein: We use zoledronic acid (Zometa) in stage IV breast cancer that has already spread to the bones. It helps prevent complications in the bones such as fractures or bone pain.

Medications for depression while on tamoxifen

Q: What medications have folks found helpful for depression post-breast cancer and while taking tamoxifen? 

Dr. Burstein: When women are on tamoxifen, we try to avoid Wellbutrin, Prozac, or Paxil because of possible drug-drug interactions with tamoxifen. Effexor (venlafaxine) is a good option for many and does not have those drug-drug interactions.

Night sweats

Question: What do you recommend for helping with night sweats? 

Dr. Burstein: Hopefully they will fade out over time. Some of the newer SSRIs such as venlafaxine can reduce hot flashes and night sweats. Prozac and Paxil do so, too, but these interfere with tamoxifen metabolism.

Node dissection, snb and axilla radiation

Q: I have Stage IIb breast cancer, invasive ductal carcinoma Grade 1, ER+, PR+, HER2-negative, just finishing neoadjuvant chemotherapy (AC → T), lumpectomy scheduled for December, 3 weeks after last Taxol treatment. I had a lymph node biopsied before diagnosis, metastatic ductal carcinoma. A PET CT showed just this one node hypermetabolic before the start of chemo. Now the node is not palpable and the primary tumor has shrunk considerably, making a lumpectomy recommended. Is it best to have a node dissection, or is it possible to start with a sentinel node biopsy? And what about axilla radiation? 

Dr. Burstein: This is a tough one to answer online because the issues are very specific. However, if the node has resolved, we often do the sentinel nodes but not an axillary dissection, and discuss extra radiation fields with the radiation team.

Neuropathy from Taxol

Q: I am starting to experience neuropathy (my oncs say it is from the Taxol). Is there anything that can help with the neuropathy? 

Dr. Burstein: Neuropathy is a common side effect related to Taxol chemotherapy. There is no well known treatment for it. Reducing the dose of Taxol can reduce the effect. There are anecdotes to suggest that glutamine supplements may minimize neuropathy, and some people say neurontin reduces the symptoms.

Extending duration of Arimidex

Q: What is the current thinking on extending the length of Arimidex past 5 years after early-stage breast cancer, lumpectomy and radiation or resuming after previously stopping at 5 years and any know benefits/risks? 

Dr. Burstein: There are no data for using aromatase inhibitors for durations longer than 5 years, nor for resuming after interruption. I tell my patients to anticipate about 5 years of an AI. There are data that longer durations of treatment built on many years of tamoxifen therapy and then continued tamoxifen or switching to an AI is clinically valuable. However, we don't know if the same rules hold for AI-based therapy.

Alcohol consumption and breast cancer recurrence risk

Q: I've heard differing opinions about acceptable levels of alcohol intake/amounts that may increase risk of recurrence. Is complete abstinence really necessary? Wine with meals is customary in my family. I'd like to set a limit without cutting it out entirely. 

Dr. Burstein: "Everything in moderation." There are data that excessive alcohol consumption – average more than a few drinks every day – is probably risky from a breast cancer point of view. It is probably risky from a lot of other points of view, truth be told. Having said that, a drink or two, once in a while, poses no real problems for breast cancer survivors.

Monitoring the effectiveness of tamoxifen

Q: If I understand correctly, there is currently no way to test whether tamoxifen is being effective or not? 

Dr. Mayer: There is no testing that we can do to check if an adjuvant therapy like tamoxifen or chemotherapy is "effective." We know from trials of thousands of women that those who pursue recommended contemporary therapies have better outcomes than those receiving older therapies, but for an individual person, we currently do not have a method to check on the status of the therapy against the cancer.

Treatment options when experiencing side effects

Q: I have Her2 breast cancer, had left breast removed and 11 lymph nodes, 9 were cancerous. I did chemo Adriamycin/Cytoxan, Taxol/Herceptin. However, my oncologist had to stop the treatment when I was about to do Herceptin alone. It was affecting my heart. I took PET scan, mammogram, ultrasound, etc., which showed cancer was gone. However, doctor says this is an aggressive form of cancer which can return anytime. They started me on radiation on the area where the cancer erupted. Then the oncologist will decide whether to give me the cancer pill Xeloda. My question is: are there any other chemo drugs that I can use that would not affect my heart? 

Dr. Mayer: Good work getting through all of that treatment! We do watch the heart carefully during Herceptin-based therapy, and in some women a drop in heart function is seen. Changes in heart function related to Herceptin can be reversible, and can get better with a break from Herceptin and use of heart medications. I usually work together with heart specialty doctors (cardiologists) to help treat changes in heart function with Herceptin, and if heart function improves, we carefully start the Herceptin again.

Using Xeloda in this situation is not supported by any data and is not recommended; therefore, instead I would suggest trying to get back on Herceptin. If the heart function does not come up enough to try again, we do have data that even just 9 weeks of combination treatment with Herceptin and chemotherapy may provide substantial benefit, so you can feel confident that you have already received excellent therapy for your cancer.

Lower doses of tamoxifen

Q: What are the risks of using a lower dose tamoxifen, i.e., 5 or 10 mg instead of 20 mg? I have stage I breast cancer [one 6mm tumor in one lymph node] and only weigh about 115 lbs. The tamoxifen is affecting my quality of life with hot flashes and night sweats. 

Dr. Mayer: The trial data supporting the use of tamoxifen as adjuvant therapy used the standard dose of 20 mg a day in everyone; we do not have data that using a lower dose will provide the same benefits. Before considering a lower dose, I would suggest maximum supportive care for side effects, including use of medications for hot flashes, or changes in how you take the medication (try taking at opposite time of day, or take as 10 mg twice a day) .

Joint and muscle pain while on Femara

Q: How do you know if joint/ muscle pain is a side effect from Femara or a symptom of bone mets? 

Dr. Mayer: Joint stiffness and pain are common side effects of aromatase inhibitors, including Femara (letrozole), and can affect up to half of the people taking the medication. If someone is having these symptoms on an AI, it is much more likely to be due to a drug side effect and not recurrent cancer. If symptoms worsen significantly and are interfering with your ability to get things done every day, then you should talk to your doctor about managing these symptoms and whether further workup is necessary.

Duration of treatment

Q: I am premenopausal and have been doing a combo of Zoladex and Arimidex since a very small recurrence in 2010 (Tamoxifen did not work for me). My doctor doesn't give me an end date for this therapy; should I be doing this until menopause? I am 43 and was originally dx with stage 2A ER/PR+ in 2007. (Had chemo, lumpectomy and radiation in 2007; mastectomy in 2010). 

Dr. Mayer: You might consider being on the Zoladex and Arimidex for at least 5 years (i.e., until 2015), then discuss with your doctor if further therapy is necessary.

Triple-negative breast cancer treatment options

Q: My sister is triple-negative, BRCA 1, dpd deficient and had 2 recurring tumors. One removed, the other under her arm, which the docs cannot remove, as it is too near her heart and wrapped round lymphs. All chemo's to date making her very ill, bowel affected because of dpd deficiency, and planter syndrome, etc. They have stopped chemo now and trying radiotherapy next week. Is there anything else we should be thinking of? 

Dr. Mayer: There are many chemotherapies with activity against triple-negative breast cancer, and cancers with BRCA1/2 mutations may be especially sensitive to certain chemotherapies. If she has had toxicities with some chemotherapies, there should be other options that she could try down the line that have a different toxicity profile and may be more tolerable, or could be used at reduced dose. Also, there is considerable research ongoing now looking into special medicines to treat BRCA1/2-associated breast cancers, and your sister should consider looking into clinical trials.

Xgeva and Zometa

Q: I am on Xgeva for my bones – is that a good drug for this too, or should I be on zometa? 

Dr. Mayer: Both Xgeva (denosumab) and Zometa are drugs approved to help prevent problems, such as pain or risk of fracture, related to having breast cancer metastatic to bones. If you are doing well on Xgeva, you do not need to be changed to Zometa.

Learn more about Drs. Burstein and Mayer, and Dana-Farber's Susan F. Smith Center for Women's Cancers: 

Harold J. Burstein, MD, PhD
Erica L. Mayer, MD, MPH
Susan F. Smith Center for Women's Cancers 

The information contained above is general in nature and is not intended as a guide to self-medication by consumers, nor is it meant to substitute for advice provided by your own physician or other medical professional. 


 
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