The Latest News In Breast Cancer Treatment

By: Maura N. Dickler, MD
Keeping track of the latest research in the field of breast cancer is an important part of working with your doctor to choose an effective treatment approach. The good news is that our understanding of this disease has grown significantly over the past decade. Several recent studies point in particular to the promising results of hormonal therapies, which can be utilized in both patients with advanced breast cancer, and those still in early stages.
For many women, the challenge of fighting breast cancer lies not only in the disease itself, but also in learning how to handle the emotional and physical strains that often accompany treatments such as surgery and chemotherapy. Most women therefore find it a relief that hormone therapy-which can be an important part of breast cancer treatment-is usually quite easy to bear.

Below, Dr. Maura Dickler of the Memorial Sloan-Kettering Cancer Center offers a basic introduction to hormonal therapy for breast cancer, as well as discussing the latest research developments.

First, can you give us a general definition of hormonal therapies for breast cancer, and explain how they work?
The term hormonal therapy describes a number of different treatment approaches, but the underlying idea is to reduce the supply of estrogen to the tumor. We can accomplish this in a number of ways by using various hormonal manipulations. The SERMs, or selective estrogen receptor modulators, interfere with estrogen at the level of estrogen receptor binding, and tamoxifen is the best known drug in this class. The aromatase inhibitors are another class of drugs that reduce blood levels of estrogen in post-menopausal women. These drugs inhibit the production of estrogen that takes place in the muscle and fat of women that continues after menopause. In pre-menopausal women, estrogen production happens mainly in the ovary, and reducing ovarian estrogen production in these women can serve as a treatment for breast cancer. This can be accomplished by either surgery or medication (e.g. the LHRH-agonists).


And why does estrogen play such a central role in breast cancer?
Well, about two thirds of breast tumors 'express', or make, the estrogen and/or the progesterone receptor. A tumor that's estrogen or progesterone receptor positive is considered 'hormone sensitive', and women who have these tumors have the option of hormonal therapy for both the treatment of early stage and metastatic cancer.

Are hormonal therapies effective in both pre- and post-menopausal women?
Yes. Hormonal therapy can be used in both pre- and post-menopausal women, but they are used a little bit differently in each group. Tamoxifen (one of the SERMS) is used in both pre- and post-menopausal women. Aromatase inhibitors, on the other hand, are more effective in post-menopausal women because they only target the non-ovarian production of estrogen. In pre-menopausal women, most of the estrogen is produced by the ovaries, so aromatase inhibitors are only useful in pre-menopausal women if ovarian production of estrogen is stopped first. This can be done by surgery (removing ovaries), radiation (destroying ovaries) or chemically (LHRH agonists like goserelin or buserelin).
What is the ATAC trial, and why is it so significant?
The ATAC trial is the first adjuvant hormonal therapy trial to be reported involving an aromatase inhibitor. It involved more than 9,000 women, and approximately 20 percent of these women had received prior chemotherapy in addition to hormonal therapy as part of their post-operative treatment. Therefore, the majority of women in this trial received hormonal therapy as their only postoperative treatment, which is not the typical scenario for the majority of women treated in the United States. The women in this trial were randomly divided into three groups. One group was given tamoxifen, another anastrozole (an aromatase inhibitor), and the third group was given a combination of anastrozole and tamoxifen.

After a 33-month follow-up period, researchers found that women who were given anastrozole had an improved disease-free survival over the groups who were given either tamoxifen or the combination of tamoxifen and anastrozole. Also, anastrozole further reduced the number of contralateral breast cancers (when cancer spreads to the other breast) when compared with tamoxifen, which is important, since we know that tamoxifen also reduces the number of contralateral breast cancers. The results were really above and beyond what tamoxifen was able to achieve in the contralateral breast, and I think it's very promising for the future

And side-effects?
Anastrozole had different side-effects than tamoxifen in the ATAC trial. Although anastrozole left more women feeling achy in their muscles and joints compared with tamoxifen, fewer women experienced hot flashes, blood clots, vaginal bleeding, or endometrial cancer.


These aromatase inhibitors have been standard care for late stage cancer, but do you foresee that they will become standard care for early stages?
Tamoxifen has been around since the late 1970s, and has been the gold standard in the postoperative adjuvant setting, and the long-term effects of tamoxifen on bone density and cholesterol have been well characterized. I think that the aromatase inhibitors hold much promise for the future, but we await long-term safety data, particularly with regards to bone density and risk of osteoporotic fractures, before changing our standard of care. Anastrozole, however, now offers another option for hormonal therapy in the adjuvant setting for women who have a contraindication to taking tamoxifen (e.g. history of blood clots or high risk of stroke). Other trials using aromatase inhibitors either after tamoxifen or instead of tamoxifen are presently ongoing, and these trials will help us determine the optimal post-operative hormonal therapy in the near future.

Do you think that the role of chemotherapy will change as hormonal therapies become more advanced?
No. I would say at the present time, there really remains a role for both chemotherapy and hormonal therapy. I think that the aromatase inhibitors will add to the proven benefits of chemotherapy instead of replacing chemotherpy. The majority of women with breast cancer will have chemotherapy followed by hormonal therapy.

Do you find that hormonal therapies are changing the way you treat patients, and is it exciting to you?
Oh, it's very exciting, yes. It's wonderful to delay chemotherapy in the metastatic setting and to give therapies that are equally effective but with fewer side-effects. With more data, I suspect that the aromatase inhibitors will be used more frequently in the adjuvant setting, and I hope that this will continue to improve the trends for improved survival in women diagnosed with this disease. There are trials presently ongoing or in the planning stages that will look at the aromatase inhibitors as drugs for breast cancer prevention as well, which is also very exciting.

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