Aromatase Inhibitor Therapy: How Long Is Best

Ever since aromatase inhibitors (AIs) began to be prescribed for post-menopausal women with estrogen receptor (ER) positive breast cancers, there has been research and no definitive answer on duration. There likely will never be a one size fits all strategy.

Identifying and sticking with the best possible treatment for your cancer is a conversation to have with your doctor.

A little background: as is always true in the development of possible new cancer treatments, the aromatase inhibitors were first approved for care of women with metastatic ER-positive breast cancers in 1995 and 1996. This is the usual pattern; drugs are first tested on people with advanced cancers and then, often, moved earlier in care. Arimidex was first approved for use in the adjuvant setting (meaning for women with early-stage ER-positive breast cancers) in 2002.

There are three AIs that are close cousins with small chemical differences: Arimidex (anastrozole), Aromasin (exemestane), and Femara (letrozole). Medical oncologists often have personal preferences based on their own experiences, and sometimes women fare better with one than with another. By that, I don’t mean that one is more effective, but that sometimes a woman has side effects that disappear if she switches to another AI. When used in the treatment of metastatic/Stage IV breast cancer, the AIs are used serially. That is, one is prescribed until it has stopped being useful, and then the patient moves on to another. In this case, there is no suggested duration of care. The AI is prescribed for as long as it is effective.

In the beginning of hormonal or anti-estrogen treatments for ER-positive breast cancers, there was Tamoxifen which has been around for more than 40 years. Before the AIs, it was the drug of choice for all women with ER-positive breast cancers. As time passed and more research was done, it was found that Tamoxifen is most effective for pre-menopausal women, while the AIs are most effective for post-menopausal women. Since Tamoxifen was generally prescribed for five years, the AIs began with that schedule, too

As we all know, breast cancer chemotherapy often induces menopause in women some years before it would have naturally happened. If their cancer was diagnosed while they were still having periods, they are considered to have pre-menopausal breast cancer. For this group, the initial strategy was two years of Tamoxifen and then, once certain they were post-menopausal, transitioning to an AI for another three years. Older post-menopausal women just began with an AI.

A new study was presented at the virtual annual congress of the European Society for Medical Oncology and published simultaneously in Lancet Oncology. The finding was that five years of extended treatment with the AI letrozole significantly improved disease-free survival (DFS) when compared with two to three years of an AI post Tamoxifen. After a median follow up of almost twelve years, the DFS rates were 67% in women who had five years of the AI vs. 62% of women who stopped after two or three years. The twelve-year overall survival rates were 88% in the longer duration group vs. 84% in the other.

The researchers commented that the optimal duration of AI therapy is still unclear as other studies continue to explore the issue. Two earlier long-term trials, the IDEAL and ABCSG-16, did demonstrate that extending the AI therapy for ten years was not better than seven to eight years.

Were you to talk with eight women who are taking one or another of the AIs, you likely would hear eight different stories and treatment plans. Some women can’t wait to stop taking the medication while others would love to stay on it forever. For most women, the hardest part about any of the hormonal therapies is remembering to take the pill each day. For some women, the cost is an issue, and is considered a primary reason for non-compliance. For others, the common side effect of muscle/joint aches and pains is difficult. When I speak with someone who is struggling with one of these drugs, I remind her how effective they are. Generally speaking, any of the hormonal treatments cut the recurrence risk by 50%. That’s a lot.

Like everything else in Cancer World, there is no simple answer. Identifying and sticking with the best possible treatment for your cancer is a conversation to have with your doctor.