Chemotherapy and Tamoxifen for Early-Stage Disease

Chemotherapy and Tamoxifen in Women with Early-Stage Breast Cancer Reduce Recurrence and Improve Survival 15 Years Later

Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Lancet, May 14, 2005

Is this for me? If you want to know if the long-term benefits of chemotherapy or tamoxifen are worth the side effects, you might want to read this article.

Background and importance of the study: Many women with early-stage breast cancer have surgery as their first treatment. Then they get other, "adjuvant" treatments such as chemotherapy and hormonal therapy in case any cancer cells were left behind—like adding an extra insurance policy after surgery.

Deciding on a treatment plan after surgery can be scary and overwhelming. You may wonder why you even need any more treatment, particularly if your surgeon said, "I was able to remove the whole cancer." Your surgeon probably did remove everything he or she could feel or see. But cancer cells can wander away from the main cancer and may even go elsewhere in the body. The risk of this happening depends on the full results of your pathology report.

You want to do whatever you reasonably can to reduce the risk of ever having the cancer come back. But you may be worried about whether the side effects of more treatment will make you feel sick or tired or make your hair fall out.

Your doctor might say, "You definitely need chemotherapy. We're dealing with a serious cancer and we need to fight back with a serious form of treatment." But suppose your doctor says, "You're in the gray zone. Your outlook is already very good. Adding chemotherapy (or tamoxifen) will make your very good prognosis a little bit better." The question then becomes: What's your personal style of making decisions? How hard do you want to push to improve your chances of doing well? Do the benefits of the treatment outweigh the possible side effects of chemotherapy or of tamoxifen?

In the study reviewed here, the Early Breast Cancer Trialists' Group (EBCTCG) looked at a very large number of women who had a variety of treatments after surgery for breast cancer. Some received chemotherapy, others tamoxifen, and others chemotherapy AND tamoxifen. A smaller number of women received another hormonal therapy known as ovarian shut-down. Chemotherapy and hormonal treatment are systemic therapies, which mean they affect the whole body through the bloodstream.

Funded by part of Oxford University, the EBCTCG analyzes data from a number of research studies around the world and then reports its findings every five years. The study reported here looks at the effects of chemotherapy and hormonal therapy after 15 years.

Study Design: The EBCTCG analyzed data from 145,000 women with early-stage breast cancer. This is the largest analysis done of women undergoing cancer treatment. The women were part of 194 randomized research studies on adjuvant chemotherapy and hormonal therapy that had started by 1995. In a randomized study, participants are assigned by chance to separate groups that compare different treatments.

All the studies were different in some ways, but they did have similarities. Many of the studies involved:

• CMF chemotherapy (cyclophosphamide, methotrexate, and fluorouracil),
• anthracycline-based chemotherapy combinations such as FAC (fluorouracil, doxorubicin, and cyclophosphamide) or FEC (fluorouracil, epirubicin, and cyclophosphamide),
• tamoxifen, or
• ovarian shut-down through surgery, radiation, or drugs.

None of these studies used:

• taxanes (brand names include Taxol and Taxotere),
• trastuzumab (brand name: Herceptin),
• raloxifene (brand name: Evista), or
• aromatase inhibitors (brand names: Arimidex, Femara, and Aromasin).

The researchers analyzed all studies that lasted longer than one month and compared the results of:

• chemotherapy with one drug versus no chemotherapy; or
• chemotherapy with two or more drugs versus no chemotherapy; or
• anthracycline-based chemotherapy with one or more other drugs versus CMF chemotherapy; or
• chemotherapy with more than one drug for longer versus shorter time periods; or
• tamoxifen versus no tamoxifen; or
• tamoxifen for longer versus shorter time periods; or
• ovarian shut-down (in women younger than 50) versus no ovarian shut-down.

The study group gathered information on every woman in every eligible study, including:

• the kind of treatment she was given;
• the date she began taking part in the study;
• her age;
• her menopausal status when she entered the study;
• her lymph node status;
• her hormone receptor status;
• whether the cancer came back in the same area (called "local recurrence");
• whether the cancer came back in another area (called "distant recurrence");
• whether cancer was found in the other breast;
• whether another type of cancer was found; and
• whether or not the woman was still living.

Results: The researchers found that chemotherapy and hormonal therapy after surgery were clearly beneficial for women with early-stage breast cancer. In particular:

• Six months of anthracycline-based chemotherapy improved the survival rate by 38% in women younger than 50 and by 20% in women between 50 to 69, compared to women who had no chemotherapy. (There were too few women 70 or older in these studies to judge what benefits chemotherapy might offer this older age group.) The improvement with chemotherapy was not affected by hormone receptor status, lymph node status, or tamoxifen use. These differences were significant, which means that the greater survival rates were most likely due to the chemotherapy and not just to chance.
• Anthracycline-based chemotherapy was significantly more effective than CMF chemotherapy.
• In women with estrogen-receptor-positive cancer, five years of tamoxifen significantly improved the survival rate by 31%, regardless of age or use of chemotherapy, compared to women with estrogen-receptor positive cancer who did not take tamoxifen.
• In women with estrogen-receptor-positive cancer, taking tamoxifen for five years significantly improved survival and reduced recurrence (the cancer coming back) compared to taking it for only one to two years.
• Ovarian shut-down significantly improved survival, but only when other systemic treatments weren't used.
• In women younger than 50 with early-stage, estrogen-receptor-positive breast cancer, receiving anthracycline-based chemotherapy for six months and taking tamoxifen for five years improved survival rates by about 50% compared to women who had no chemotherapy or tamoxifen.
• In women 50 to 69 years old with early-stage, estrogen-receptor-positive breast cancer, receiving anthracycline-based chemotherapy for six months and taking tamoxifen for five years improved survival rates by about 40% compared to women who had no chemotherapy or tamoxifen.

Conclusions: The researchers concluded that six months of anthracycline-based chemotherapy followed by five years of tamoxifen improves survival rates by about 50% in women younger than 50 with early-stage, estrogen-receptor-positive breast cancer (the most common type). In women 50 to 69 years old with the same type of cancer, the same treatment plan improved survival rates by about 40%. In both cases the improvement is in comparison to women who had no chemotherapy or tamoxifen.

Take-home message: The study reviewed here is very large and looked at outcomes after a long time—15 years—so the results provide strong and reliable evidence about the value these treatments offer your whole system. These results reinforce earlier research that show the benefits of chemotherapy and tamoxifen after surgery for women with early-stage, estrogen-receptor-positive breast cancer.

Choosing to take any strong medicine such as chemotherapy or tamoxifen always means having to weigh its benefits against its side effects. This study shows that the potential benefits of chemotherapy, especially anthracycline-based chemotherapy, and five years' worth of tamoxifen are substantial. Women younger than 50 had the biggest benefit from chemotherapy, but women between 50 and 69 still had good results. The study didn't include enough women over 70 to draw any conclusions for that age group.

This study also shows the benefits of anthracycline-based chemotherapy (Adriamycin is one of the most common anthracycline chemotherapy drug) over CMF chemotherapy. And it reinforces research showing that taking tamoxifen for five years is better than taking it for only one or two years.

These studies give us an important long-term perspective: The benefits of chemotherapy and hormonal therapy really do last a long time. The drugs used in these studies are very good medicines, and they are still used today. Newer drugs, such as Herceptin and aromatase inhibitors, may offer even more benefits, leading to further long-term improvement.

It takes a big commitment to go through chemotherapy and five years of daily tamoxifen. If the long-term benefits are real and significant, you're much more likely to make and fulfill this commitment. While the benefits described here are very impressive, Taxol, Herceptin, and aromatase inhibitors are examples of newer treatments offering even more promise.

With so many options, it can be tough to choose the best breast cancer treatment for YOU. No one type or combination of treatments is best for all women. More research is needed on the long-term safety and effectiveness of newer drugs such as Herceptin and aromatase inhibitors and how they compare to results with chemotherapy and tamoxifen. Stay tuned to breastcancer.org for the latest information on these new treatments.

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