October 2011 Ask the Expert: Metastatic Breast Cancer Treatments and Strategies
During the month of October, Living Beyond Breast Cancer expert Erica L. Mayer, MD, MPH, answered your questions about new treatments and research for metastatic breast cancer and how to enhance your quality of life while living with metastatic disease.
In general, there are a number of choices for endocrine therapy: non-steroidal aromatase inhibitors (AI) such as anastrozole (Arimidex) and letrozole (Femara), steroidal aromatase inhibitors such as exemestane (Aromasin), tamoxifen, and fulvestrant. All of these agents are very active against metastatic breast cancer. Selecting which agent to use often depends on prior exposures—for example, did the tumor recur while the woman was taking one of these therapies and would then be considered resistant? Or, does the woman have a preference for oral versus injection therapy?
For a woman whose tumor progresses on anastrozole, options include tamoxifen, exemestane or fulvestrant. The question of exemestane versus fulvestrant has specifically been addressed in a clinical trial in which women progressing on a non-steroidal AI were randomly selected to get either exemestane or fulvestrant. Results from that study showed no difference in outcomes between the arms. Therefore, a decision in this setting should be made based on a woman’s preference for method of administration, and the woman can feel confident that either choice is acceptable.
Dr. Mayer: The study of both cancer stem cells and cancer vaccines is of significant interest, and multiple laboratories worldwide are investigating these topics. Much of this work has broadened our knowledge of cancer cell biology but has not yet translated into findings with a direct impact on women and their treatment.
There are many other important areas of breast cancer research as well. Other topics pursued in research laboratories include learning more about how cells respond to growth signals, understanding how to target the communication that happens inside cancer cells and learning more about how cancer cells interact with their environment inside the body.
Clinical research areas of interest include evaluating the safety and activity of new cancer therapies as part of clinical trials, and exploring the effect of a breast cancer diagnosis and subsequent treatment on a woman's quality of life and emotional status. Population studies look at possible reasons people develop cancer and try to identify activities which can be protective against cancer. All of these arenas are important cancer research topics and can lead not only to better understanding of cancer biology, but also to improvements in cancer prevention and treatments.
Dr. Mayer: Congratulations on doing very well! The use of trastuzumab (Herceptin) for HER2-positive breast cancer has certainly revolutionized the treatment of stage IV (metastatic), HER2-positive breast cancer, and increasingly we see women with HER2- positive cancer who are living and thriving with advanced disease. Therefore, your question about duration of trastuzumab is increasingly common.
Unfortunately, we do not currently have data from clinical trials to guide these decisions. In practice, many of us will continue trastuzumab indefinitely in the setting of metastatic, HER2-positive disease. We also continue cardiac monitoring, often on an every 4-6 month basis. Anecdotally, there does not appear to be any long-term toxicity from extended exposure to trastuzumab. Therefore, I would suggest continuing with trastuzumab for now, and I wish you best of luck with your treatment!
Dr. Mayer: Being diagnosed with metastatic breast cancer is a life-altering experience; it often feels like an emergency requiring immediate action. Occasionally there are situations when beginning therapy right away is necessary. However in the majority of situations, there is usually adequate time to learn more about the new diagnosis and visit with doctors while making a decision about how to proceed. This process can also include getting second opinions regarding treatment options or taking time to consider enrolling in a clinical trial.
Overall, it can be worthwhile to take time to learn about your treatment choices and become fully educated. However, as each woman’s situation is different, there should be ongoing discussion with your doctor about the safety of waiting before making a final decision.
One of the most important things to start with is good communication with your treatment team as well as at home with your friends and family. You want to make sure everyone knows your preferences, values and goals as you make decisions together.
It’s important to feel well-informed. Although the Internet is full of cancer information, you have to use it wisely and try to stay with sites that are safe and reviewed by cancer specialists.
Always consider getting a second opinion if you are confused about what to do next. Your own doctor will not be offended if you visit with another specialist, and often an outside opinion can help put things in perspective.
Ultimately, there are often many treatment options available for metastatic breast cancer. Being well-informed and communicating with your treatment team can often lead to effective and satisfying decisions.
Dr. Mayer: In general, you will want to try to stay on therapies for as long as possible to get maximum benefit. Indications that it’s time to change therapies include clear evidence of cancer progression, either on a scan or because of worsening symptoms, or the development of unbearable side effects which cannot be fixed.
Although monitoring tumor markers or other blood tests to determine cancer status can help gauge the effectiveness of a therapy, decisions about whether or not to change treatments should not be based entirely on trends in markers. Some chemotherapies such as doxorubicin (Adriamycin) can have increasing toxicity which can result in permanent body damage over time. But for most chemotherapies, including paclitaxel, treatment can continue until it no longer works or until a side effect such as neuropathy makes it too difficult to continue the medication.
Dr. Mayer: Although the outcome of research on the agent iniparib has been disappointing, other PARP inhibitors, including veliparib and olaparib, continue to be studied in both triple-negative breast cancer and in cancers that develop in women with BRCA1 or BRCA2 gene mutations. Other targeted agents under study for triple-negative breast cancer include treatments that block cell surface receptors, specialized proteins that take part in communication between the cell and the outside world, or therapies that disrupt communication inside cancer cells.
There is also interest in examining the activity of certain types of chemotherapies, including “platinum” chemotherapy, for triple-negative breast cancer. The majority of this work is being done in clinical trials; therefore women with triple-negative breast cancer are strongly urged to enroll in a trial to get exposure to these new medications.
Dr. Mayer: Congratulations on 6 years living with metastatic breast cancer! It sounds like you have done well on your treatments to date.
As you mention, liver directed therapies, local therapies directed to metastatic cancer spots in the liver, have a well-defined role in the treatment of some solid tumors, notably colon cancer. The possible benefit of liver-directed therapy in metastatic breast cancer is not well studied.
Some data have been published describing small numbers of women who have received tumor ablation for treatment, however these studies contain no appropriate comparison group. Therefore it is not known if having treatment to the liver improves outcomes for these women versus continuing on with more traditional treatments such as chemotherapy.
In general, liver-directed therapies outside of a trial are not encouraged, especially not while receiving bevacizumab, which could increase the risks associated with the procedure. But you should feel comfortable discussing this topic in further detail with your cancer doctor.
Dr. Mayer: Congratulations to you as well on 9 years of living with metastatic breast cancer!
Whenever there is a new finding on scans, it’s important to consider all treatment options. Chemotherapy for metastatic breast cancer is usually a very different experience compared to receiving adjuvant chemotherapy after surgery. Chemotherapy dosing and scheduling for metastatic disease are designed to maximize treatment activity against the cancer while minimizing any side effects related to the treatment. This often includes schedules offering small doses on a weekly schedule.
If significant side effects develop, changes in dose and schedule often can overcome them. If not, moving to an agent with a different side effect profile can help. Also, changes in heart function related to trastuzumab appear to resolve once treatment is held. Rechecking heart function would be important to do right now.
Treatment options for HER2 positive breast cancer continue to evolve, and many new targeted biologic agents are available as part of clinical trials. It is important to review with your doctor what treatments are available to you at this time and what opportunities exist through clinical trials.
Dr. Mayer: Capecitabine is a fine choice for metastatic lobular carcinoma and can often be quite effective. Close monitoring by bloodwork, visits with your treatment team for examination andperiodic radiology scans sound like a very appropriate start. Once you are settled into treatment and tolerating it well, you could consider decreasing the frequency of bloodwork to every 3-4 weeks. Restaging every 3-4 months is acceptable as well.
Dr. Mayer: In general, basic supplements, including multivitamins, calcium, and standard dose vitamin D, are fine to take during chemotherapy. Some supplements or high dose vitamins have the potential to negatively interact with traditional cancer medicines. Additionally, exposure to some supplements can irritate the liver, making it harder to safely administer chemotherapy.
It is very important to report any supplements you are taking to your doctor so you can work together to ensure that taking the supplements in combination with chemotherapy is safe.
Dr. Mayer: When a woman is premenopausal, exposure to chemotherapy can affect ovary function, causing a change in the timing and nature of periods. Depending on a woman’s age and type of chemotherapy exposure, there is a chance that chemotherapy can lead to temporary or permanent menopause. If the effect is temporary, periods can be irregular after the ovaries wake up and may or may not eventually return to normal cycles. If a woman has very heavy vaginal bleeding, evaluation by a gynecologist is suggested.
Dr. Mayer: Primary endocrine therapy choices for hormone receptor- positive breast cancer include non-steroidal aromatase inhibitors (anastrozole, letrozole), steroidal aromatase inhibitors (exemestane), tamoxifen and fulvestrant. Megestrol (Megace) is occasionally considered, however it sometimes can cause undesirable side effects.
Outside of clinical trials, women often transition to chemotherapy after finishing these endocrine therapies. However a growing number of clinical trials add new oral biologic therapies to previously used endocrine therapy in order to overcome tumor resistance. Alternatively, some trials offer treatment just with an oral biologic agent without the use of chemotherapy. Therefore, you could seek out trial enrollment as a next step after progression on letrozole.
Dr. Mayer: Congratulations on doing so well for 4 years and counting! Determining life expectancy with metastatic breast cancer is tricky, as population statistics may not reflect what happens to an individual person. Furthermore, the ongoing development of better therapies for metastatic breast cancer has definitely led to improvements in survival.
We increasingly are seeing women do well for much longer than expected. In general, it is not possible to give updated life expectancy numbers, but we certainly hope that we continue to see more and more women living and thriving while being treated for metastatic disease.
Dr. Mayer: Experiencing joint discomfort while taking aromatase inhibitors is a common phenomenon; some research even suggests it may reflect favorable activity of the medicine in the body! However, managing this side effect can be challenging.
Recommended techniques include use of non-steroidal inflammatory agents, stretching, exercise and acupuncture. Ongoing investigations are looking at new complementary techniques which may be of benefit. Sometimes changing to another aromatase inhibitor can make a difference. Good communication with your doctor about your degree of discomfort will allow you to work together on the best treatment strategies.
Dr. Mayer: Management of cancer-related pain has improved over the past several years. One of the biggest improvements has been recognizing the need to monitor pain more closely. In many doctors’ offices, evaluating pain has become as commonplace as checking blood pressure.
Additionally, a multidisciplinary team approach is being used more often in pain management. This means a group of providers— including medical oncologists, oncology nurses, pharmacists, pain and palliative care specialists, radiation oncologists, and social workers—work together to manage a woman’s pain using a variety of techniques beyond just pills.
Ultimately, the most successful pain management occurs when women and their doctors are able to communicate openly and honestly about symptoms, needs and options.