Timing of Tamoxifen and Radiation Treatment after Breast-Conserving Surgery May Not Matter
Reviewed study: "Timing of Tamoxifen and Radiation Treatment after Breast-Conserving Surgery May Not Matter" by L.J. Pierce et al., Journal of Clinical Oncology, January 1, 2005; E.E.R. Harris et al., Journal of Clinical Oncology, January 1, 2005
Background and importance of the study: Adjuvant treatments are the treatments you get after surgery to lower the risk of recurrence (the chance that the cancer could come back). Hormonal therapy, radiation therapy, and chemotherapy are all adjuvant treatments.
In general, when chemotherapy is recommended, it is the first treatment given after surgery. The thinking is this: "Chemotherapy affects the whole body, wherever cancer cells might possibly be. Because distant cancer—cancer that's spread from where it started to distant organs or lymph nodes—is what's most threatening, let's give the chemotherapy first. When that's done, we'll go back to the important local treatment issues."
In certain situations, your doctor might say it's fine to give chemotherapy after radiation if the risk of cancer spread is relatively low. There might also be practical reasons for delaying chemotherapy treatment. For example, you may want to feel well and have your own real hair for your own or your daughter's wedding.
But what about the timing of HORMONAL therapy relative to radiation therapy? Is it better to give hormonal therapy (usually tamoxifen) together with radiation therapy, or start it after radiation is finished? Doctors are concerned that giving hormonal therapy at the same time as radiation therapy may decrease the benefit of radiation or increase the risk of side effects.
There haven't been many studies on this. Most studies have looked at the timing of tamoxifen and radiation. Some early research using only cells in a lab suggested that tamoxifen may reduce the effectiveness of radiation therapy. Other research suggested that giving tamoxifen at the same time as CHEMOTHERAPY reduced the effectiveness of the treatments. But other small studies have shown no differences.
In the two studies reviewed here, researchers looked at the timing of tamoxifen and radiation therapy after surgery to see if there were any differences in recurrence and survival, as well as any differences in side effects from the treatments.
Study designs: Both studies were retrospective studies. This means that researchers evaluated information on the timing of treatments for patients who had already been treated.
In the first study, the researchers from the Southwest Oncology Group used data from an earlier study for a new purpose. The researchers looked at information on women who had had breast-conserving surgery and then adjuvant (after surgery) treatments, in different orders:
- Group 1 (107 women) had radiation therapy immediately after surgery. After the women were finished with radiation, they had chemotherapy followed by tamoxifen.
- Group 2 (202 women) had chemotherapy after surgery. After they were finished with chemotherapy, they began tamoxifen and radiation therapy at the same time.
The women in the two groups were similar in terms of:
- age (under 65),
- menopausal status (about 60% were pre-menopausal), and
- breast cancer size and margins (slightly more than half had cancers smaller than two centimeters, and almost all had negative margins).
About 70% of the women in Group 1 and 50% of the women in Group 2 had cancers that were hormone-receptor-positive. This means that some women with hormone-receptor-negative cancer received hormonal therapy. The original study took place from 1989 to 1993.. Today, a study would give hormonal therapy only to women with hormone-receptor-positive disease.
The researchers followed the women for about 10 years, looking at:
- recurrence,
- disease-free survival (the women were alive and the cancer did not come back),
- overall survival (the women were alive and the cancer may or may not have come back), and
- side effects of the treatments.
In the second study, researchers looked at women with Stage I or II breast cancer who had treatment at the University of Pennsylvania. They selected information about women who had had breast-conserving surgery, radiation treatment, and tamoxifen. Some women also had received chemotherapy, and others had not.
These researchers also divided the women into two groups, depending on the order of their treatment after surgery:
- Group 1 (104 women) had radiation therapy, and then began tamoxifen.
- Group 2 (174 women) received radiation therapy and tamoxifen at the same time.
About 80% of the women in each group were hormone-receptor-positive, and about half in each group were node-positive. The women in Group 1 were older (average age about 59) than the women in Group 2 (average age about 51). Also, more women in Group 1 had chemotherapy than women in Group 2 (63% compared to 25%).
The researchers followed the women for about eight and a half years. Like the researchers in the first study, they looked at:
- recurrence,
- disease-free survival,
- overall survival, and
- side effects of the treatments.
Results: In both studies, researchers found no significant differences in recurrence, disease-free survival, and overall survival between women who received radiation therapy and tamoxifen at the same time and those who received tamoxifen after radiation therapy. In both studies there were also no significant differences between groups in side effects from treatment.
Conclusions: These studies both concluded that there seemed to be no difference in recurrence, disease-free survival, or overall survival when tamoxifen and radiation therapy were given together or when tamoxifen was given after radiation therapy. The researchers also found no differences in treatment side effects between the two groups.
Both of these studies were retrospective, and were not originally designed to address the question of treatment timing. Because of this, both groups of researchers said that a study specifically designed to address the question of treatment timing was needed.
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What breastcancer.org says about this article…
Timing of Tamoxifen and Radiation Treatment after Breast-Conserving Surgery May Not Matter
If you have early-stage breast cancer, your doctor will probably suggest that you receive different kinds of treatment, either together or in sequence, after you've recovered from surgery. These treatments can include radiation therapy, hormonal therapy, and chemotherapy—adjuvant treatments that significantly reduce the risk of recurrence (the cancer coming back). But doctors are still trying to figure out the best way to time these treatments. Should radiation be given first, then hormonal therapy? Or should they both be given at the same time?The studies reviewed here suggest that the timing of radiation therapy and the hormonal treatment tamoxifen doesn't really matter. The timing doesn't affect the cancer coming back, disease-free survival, overall survival, or treatment side effects. Still, these were retrospective studies, which mean the researchers gathered and analyzed results of old treatment information. So the value of the results is limited. The researchers had no control over many important issues such as the time intervals between treatments, the women chosen to participate, and who got what treatments and why. A randomized study is needed—one in which participants are assigned by chance to different groups.
Meanwhile, talk to your doctor about the best way to combine your treatments. Some women choose to delay tamoxifen until after radiation is done. They may want to be gentle on their bodies or approach things one step at a time. Also, if you have side effects during treatment, you'll have a better idea of what's causing them if you're only doing one thing at a time.
There's usually no rush to start on tamoxifen. Most women take hormonal therapy for at least five years, so delaying its start until after five to seven weeks of radiation treatment is no big deal. Plus, until a randomized study provides a more solid answer to this question, some radiation oncologists recommend giving radiation followed by tamoxifen. That's because one randomized study has shown better results from chemotherapy followed by tamoxifen compared to tamoxifen given during chemotherapy. This may possibly suggest a potential benefit to separating radiation and tamoxifen. On the other hand, your doctor may recommend continuous systemic medicine therapy (chemotherapy, then tamoxifen). This would mean taking tamoxifen during the time you're having radiation treatment. Doctors may feel strongly about doing this if a cancer is more aggressive or extensive.
Of course, all treatment decisions have to be customized to your unique situation. There is no "right way" to combine tamoxifen and radiation for all women. The type and combination of adjuvant treatments that are best for you depend on many different factors, including:
- personal considerations—your emotional, thoughtful, spiritual, and cultural approach to making health decisions—and practical concerns,
- your history and physical exam findings,
- the type, size, and stage of breast cancer you have, as determined by your pathology report and imaging studies,
- whether or not you've gone through menopause,
- previous treatments you've had,
- how your body reacts to each type of treatment,
- other health problems you might have, and
- other factors unique to your situation.
Talk to your doctor about which adjuvant treatments would be best for YOU.