One of the studies that has attracted the most attention at the 2014 American Society of Clinical Oncology Annual Meeting and in the media covering the meeting is a phase III trial that found giving a woman with hormone receptor negative (ER- and PR-) breast cancer goserelin (Zoladex), a drug that temporarily shuts down the ovaries, increased the odds that her ovaries would resume functioning after she completed treatment. Of the 218 women studied, 22% of those who had chemotherapy alone experienced ovarian shutdown caused by the drugs compared to 8% of the women who took Zoladex along with chemotherapy. There were 13 pregnancies among the women who had chemotherapy alone and 22 among the women who had chemotherapy and Zoladex.
Knowing that chemotherapy may keep you from being able to have a child, or more children, has often been one of the more emotionally challenging aspects of breast cancer treatment for premenopausal women. (The problem is that chemotherapy can be toxic to the eggs or put a woman into premature menopause.) Over the past five years, advocacy groups have worked hard to increase awareness about the importance of doctors talking to young cancer patients about fertility and making women aware of options like egg and embryo freezing that might help them have a child after their treatment ends. Now, women with hormone-negative tumors have a new option to talk over with their doctors: using Zoladex to protect their ovaries from chemo.
Taking Zoladex cannot guarantee chemotherapy won’t affect the ovaries. The study found that Zoladex reduced the risk of women going into premature menopause, but most of the women still did. There is currently no way to know which women are most likely to benefit from Zoladex and which will not. That said, I would encourage women who are premenopausal, have hormone-negative tumors, and are hoping to have a child after chemotherapy to talk to their doctors about this option.
You may also have heard that the researchers presented findings from an exploratory analysis that showed the women who took Zoladex appeared to have improved disease-free survival and overall survival. The researchers didn’t set up the study to look at survival, and their exploratory analysis suggests that more studies should be done to see if it is beneficial. It does not tell us that Zoladex improves survival in women with hormone-negative tumors.
Another group of researchers presented findings from two studies that looked at the use of ovarian suppression in premenopausal women with hormone receptor positive breast cancer. At the time this study was started, premenopausal women with hormone-sensitive tumors would take tamoxifen for at least five years following breast cancer surgery. But postmenopausal women were now taking aromatase inhibitors because studies had found that they were more effective for them than tamoxifen.
(Tamoxifen blocks the estrogen receptor on the cancer cells, preventing them from growing, and can be used by pre- or postmenopausal women. Once a woman goes into menopause the ovaries stop producing estrogen; but they continue to produce a precursor that the breast and other organs can convert into estrogen by using an enzyme called aromatase. The aromatase inhibitors block this enzyme. For this reason, only women who are in menopause or who have been put into temporary menopause can take an aromatase inhibitor.)
So, studies were designed to look at whether the aromatase inhibitors would be better for premenopausal women. But for a premenopausal woman to take an aromatase inhibitor, she’d first have to be put into temporary or permanent menopause. In these studies, ovarian suppression could have been through a drug (in this case, the drug triptorelin was used), oophorectomy (removal of the ovaries), or ovarian radiation. Then, women were given five years of tamoxifen or the aromatase inhibitor exemestane (Aromasin). After following the women for five years, disease-free survival among the women in the Aromasin group was 91.1% compared to 87.3% for those taking tamoxifen.
As a champion of talking about collateral damage, I would be remiss if I did not point out that the side effects were about the same in both groups. So, while the small benefit of using an aromatase inhibitor instead of tamoxifen is real, some women may decide it is not worth it for them and they should know tamoxifen remains another option.
As the hormonal options for women with estrogen positive cancers increase, it can make deciding on a treatment more difficult. It is important for women to know that there are options. Studies are designed to determine the “best” treatment. But the best treatment for you will be the one that does not sacrifice the quality of your life for a small statistical advantage. Each woman will have to have a discussion with her physician to determine the right approach for her.