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September 17, 2001
News this month
NIH recommendations on adjuvant therapy for breast cancer
Breast cancer, in its early stages, is most often treated initially with surgery. But increasingly, women are receiving additional treatments, called adjuvant therapy, in the form of chemotherapy, hormone therapy or radiation therapy. The evidence is mounting that such adjuvant therapy is helping more women survive breast cancer.
Evidence is mounting that adjuvant therapy is helping more women survive breast cancer.
A recent report from the National Institutes of Health (NIH) consensus conference outlined the ways in which adjuvant therapy should be used, the types of patients who should receive it and the forms of therapy that are beneficial. The conference brought together national and international experts to clarify key questions regarding the selection of treatments, quality of life and new research directions in adjuvant therapy. Their goal was to answer, when possible, the following questions:
- Which factors should be used to select systemic adjuvant therapy?
- Which patients should receive adjuvant hormonal therapy (such as tamoxifen)?
- For which patients should adjuvant chemotherapy be recommended? Which drugs should be used and at what dose or schedule?
- For which patients should post-mastectomy radiation therapy be recommended?
- How do side effects and quality of life issues factor into individual decision-making about adjuvant therapy?
- What are promising
new research directions for adjuvant therapy?
Types of adjuvant therapy
There are two ways in which adjuvant therapy acts—either systemically or locally.
Systemic: Systemic therapy acts on the whole body, not just one area, such as chemotherapy and hormonal therapy, typically tamoxifen.
Localized: Radiation therapy is used as a local adjuvant treatment to destroy cancer cells that might remain in the tumor location or may have spread to nearby tissues.
Panel recommendations
1) Estrogen receptors and tamoxifen
All women whose breast tumors contain estrogen receptors should consider receiving hormone therapy such as tamoxifen, regardless of:
- age,
- menopausal status,
- tumor size or
- whether the cancer has spread to nearby lymph nodes.
Five years of tamoxifen is currently the standard adjuvant hormonal therapy. There is currently no data to support the use of tamoxifen for longer than five years. The panel emphasized that hormonal therapy is not indicated for women whose tumors do not have hormone receptors.
Including anthracycline drugs as part of chemotherapy regimens produces a small but statistically significant survival advantage….
2) Lymph node status and treatment
Chemotherapy using a combination of drugs for most pre- and post-menopausal women, regardless of lymph node involvement or estrogen receptor status, was recommended. Including anthracycline drugs as part of chemotherapy regimens produces a small but statistically significant survival advantage over regimens that do not contain anthracyclines. However, there are not enough data to support the routine use of taxanes as adjuvant therapy for early breast cancer or dose-intensive chemotherapy.
3) Radiation after mastectomy
Women who have undergone mastectomy and who have four or more cancerous lymph nodes or an advanced primary tumor benefit from post-surgical radiation, the panel concluded. The panel added that it is unclear whether women with one to three cancerous lymph nodes benefit from radiation therapy and that this question should be tested in a randomized clinical trial.
4) Side effects and quality of life
Adjuvant treatments can cause serious short- and long-term side effects, such as:
- premature menopause
- weight gain
- mild memory loss
- fatigue
To assess their impact on a patient's life, the panel suggested that clinical trials involving adjuvant therapy also measure a patient's quality of life. Long-term follow-up of women in these trials will help fully understand the effects of adjuvant therapies. The continued development of decision-making tools will help patients and their physicians weigh the risks and benefits of adjuvant treatments.
More research needed
Among its other recommendations for future research, the panel called for carefully designed studies of:
- combined hormonal therapy
- hormonal therapy versus chemotherapy in premenopausal women whose tumors have estrogen receptors
- high dose chemotherapy
- taxanes
- factors that predict the effectiveness of treatments in individual patients
- new drugs
- radiation techniques that reduce the dose to normal tissue such as the heart and lungs
- the effectiveness and side effects of adjuvant therapies in women older than 70
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Why and when to use adjuvant therapy
Through continuing research into new treatment methods, women with breast cancer now have more treatment options and hope for survival than ever before. At the same time, however, deciding on therapy has become more complex. The goal of the NIH consensus panel was to shed some light on these complexities. Overall, I thought the report was a very conservative one.
"Women with breast cancer now have more treatment options and hope for survival than ever before."
The use of adjuvant therapy must be individualized for each breast cancer patient. Giving a woman one or more chemotherapy agents or hormone therapy or radiation therapy are all types of adjuvant therapy.
Deciding on adjuvant treatment
There are many things taken into consideration when deciding on a patient's course of treatment and whether it will include adjuvant therapy. We look at prognostic and predictive factors.
- Prognostic
information tells you how you would do without treatment,
what the risk of relapse is. For example, the numbers of lymph
nodes involved would be a prognostic indicator—the higher
the number, the more likely a recurrence. Other prognostic indicators
include tumor size and the pathologist's estimation of the tumor
grade.
- Predictive
factors tell how a person will do with a given therapy.
If we know a person's estrogen and progesterone receptor status,
for example, we can better judge whether giving adjuvant therapy
with tamoxifen will reduce the risk of recurrence.
"The optimal length of time to take tamoxifen is five years."
The tamoxifen debate
One point the panel made that I thought was especially important was that the optimal length of time to take tamoxifen is five years. Tamoxifen is the most commonly used form of hormonal adjuvant therapy. It is a type of anti-estrogen hormone therapy, meaning it deprives cancer cells of the female hormone estrogen, which some breast cancer cells need to grow. The NIH panel saw no benefit in taking it longer. At the same time, they found no data to support the use of the osteoporosis drug raloxifene to treat breast cancer or prevent its recurrence.
HER2/neu status
Tests can now be used to determine if a tumor overexpresses HER2, a protein. If HER2 is overexpressed, a woman's HER-2/neu status is considered positive. While the NIH panel said there was no evidence to support the use of HER-2/neu status in deciding on the course of treatment, there are others who believe cancer should be treated much more aggressively if a woman is HER-2/neu positive.
"Using more than one chemotherapy drug…is more effective than using a single agent."
Using one or more drugs for chemotherapy
Using more than one chemotherapy drug, called polychemotherapy, is more effective than using a single agent; that opinion is widely held. Giving more than one medication increases the odds of destroying all the cancer cells. However, whether these drugs should be given together or given one after the other is still an open question.
Taxanes
The NIH panel supported the use of taxanes, including docetaxel (Taxotere)
and paclitaxel (Taxol), to treat advanced breast cancers, not
early breast cancers. Readers should know that there are studies currently
being done investigating the use of taxanes as first-line therapy
for early breast cancer as well as for adjuvant therapy.
"As a greater number of years from diagnosis elapse, patients receiving more intensive approaches may have an advantage."
Intense vs. standard therapy
The NIH panel found no evidence to support the use of more dose intense therapy, such as high dose chemotherapy or stem cell transplantation. However, our own experience with these approaches has been very favorable. There are also data from the U.S. and Europe which suggest that although these approaches yield results very similar to standard therapy in the first years after diagnosis, as a greater number of years from diagnosis elapse, patients receiving more intensive approaches may have an advantage. For patients at very high risk of recurrence even after standard therapies, dose intense treatments remain an attractive alternative.
The patient's role
As you can see, there remains debate even among the experts. That does not make it easy for patients. But as an oncologist, my mandate is to talk about these options with my patients so that they understand the potential benefits as well as the drawbacks. The best treatment recommendation depends on:
- the patient's age
- type of breast cancer present
- size of the tumor
- grade of the tumor
- involvement of lymph nodes
- estrogen/progesterone receptor status and HER-2/neu status
- whether the cancer is localized or has spread.
A major reason people get a second opinion is that they are not clear on their options. It's also a good idea to see different specialists, such as a medical oncologist as well as a radiation oncologist.
Dr. Barbara Burtness is a medical oncologist specializing in breast and colorectal cancer at Yale-New Haven Hospital and is an associate professor of internal medicine and medical oncology at Yale University School of Medicine.
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