ER-Positive Tumors and Hormone Therapy My doctor recommended that I have hormone therapy before I have my surgery. I thought hormone therapy was used after surgery. Why is she suggesting I have it before my surgery? What you are describing is called neoadjuvant therapy. Neoadjuvant means "before surgery," and both chemotherapy and hormone therapy can be used as neoadjuvant treatment. When chemotherapy or hormone therapy is used after surgery, it is called adjuvant treatment.
Neoadjuvant treatment is typically used to decrease the size of a large tumor before surgery. By shrinking the tumor a woman who would otherwise require a mastectomy may instead be able to have a lumpectomy. Chemotherapy has been studied more in the neoadjuvant setting than hormone therapy has, but it certainly makes sense to use hormone therapy in this setting, since the goal is to shrink the tumor, and hormone therapy can do that without the side effects that accompany chemotherapy.
Neoadjuvant hormone therapy is only an option for women whose tumors are estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive. Typically, a woman will take hormone therapy for three or four months prior to surgery. After her hormone therapy is completed she will have a mammogram or ultrasound or both to determine what effect the hormone therapy is having and how long it should be continued. If the hormone therapy does make the tumor smaller, then a lumpectomy can be performed rather than a mastectomy. It can be exciting to see that the hormone therapy has been effective, that the tumor has responded, and that a lumpectomy can be performed. But it is also important to keep in mind that treating the tumor with hormone therapy or chemotherapy prior to removing it surgically has not been found to improve a woman's chance of surviving from breast cancer.
For premenopausal women, neoadjuvant hormone therapy can include the drug tamoxifen; the drug goserelin (brand name Zoladex), which puts a woman into temporary menopause; or oophorectomy (removal of the ovaries), which causes immediate and permanent menopause. For postmenopausal women, neoadjuvant treatment options include tamoxifen or one of the aromatase inhibitors: letrozole (brand name Femara), anastrozole (brand name Arimidex), or exemestane (brand name Aromasin).
In 2001, researchers reported in the Journal of Clinical Oncology that a study comparing Femara to tamoxifen in the neoadjuvant setting found Femara to be more effective. In this study 128 women who were ineligible for breast-conserving surgery because of the size of their tumor were randomized to either Femara or tamoxifen for four months. The study found that 69 (48 percent) of the women who received Femara were able to have breast-conserving surgery following their neoadjuvant treatment compared with 45 (36 percent) of the 126 women who received tamoxifen.
In 2003, at the San Antonio Breast Cancer Symposium, researchers from the United Kingdom presented the results of the IMPACT trial, which evaluated three different hormonal strategies in the neoadjuvant setting. This trial randomized 330 postmenopausal women with ER-positive tumors at least 2cm in size to Arimidex or tamoxifen, or Arimidex plus tamoxifen for three months prior to surgery.
The study found that the tumors responded equally well—response was measured as at least a 50 percent reduction in size—to Arimidex and tamoxifen or the combination of the two. The response rates were 37 percent for Arimidex, 36 percent for tamoxifen, and 39 percent for the combination.
The study also suggested that women with HER2-positive tumors may respond better to Arimidex than tamoxifen, as 58 percent of the HER2-positive women responded to Arimidex, compared with 22 percent of the women on tamoxifen and 31 percent of the women on the combination treatment. (HER2 is also sometimes referred to as HER-2 or Her-2/neu or erb-b2.) However, this analysis was based on only 34 patients, which is too small of a number to allow us to say one drug is better than the other. This finding does, however, support findings from the Femara trial, which found that women who were HER2-positive did better on Femara than on tamoxifen.
The question that you need to consider before starting neoadjuvant hormonal therapy is whether you would prefer to have a lumpectomy followed by radiation, or a mastectomy. If you want to try to give yourself the option of having a lumpectomy, then you should try the hormone therapy. If it is okay with you to proceed directly to a mastectomy, then you can forgo the hormone therapy or more likely have it after surgery. The other advantage of neoadjuvant therapy is that you can see if the tumor is responding to the particular therapy. If it does not shrink, that may mean that you should try a different drug.
If you decide to have the neoadjuvant hormone therapy, you and your doctor can determine which one is best for you. Although more research is still needed, it does appear that Arimidex or another aromatase inhibitor may be a better option for postmenopausal women who are HER2-positive. So, if your tumor is HER2-positive, you should also factor that into your decision.
Ellis MJ, Coop A, et al. Letrozole Is More Effective Neoadjuvant Endocrine Therapy Than Tamoxifen for ErbB-1- and/or ErbB-2-Positive, Estrogen Receptor-Positive Primary Breast Cancer: Evidence from a Phase III Randomized Trial. Journal of Clinical Oncology 2001 Sep 15;19(18):3808–16.
Smith I, on Behalf of the IMPACT Trialists. Comparison of Anastrozole vs. Tamoxifen Alone and in Combination as Neoadjuvant Treatment of Estrogen Receptor-Positive (ER+) Operable Breast Cancer in Postmenopausal Women: The IMPACT Trial. 26th Annual San Antonio Breast Cancer Symposium, Abstract 1. Presented Dec. 3, 2003.
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