Is Switching Hormonal Therapies Better Than Taking Only One?

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Many postmenopausal women take hormonal therapy medicine -- either an aromatase inhibitor or tamoxifen -- for 5 years after surgery and other treatments for hormone-receptor-positive, early-stage breast cancer. Hormonal therapy reduces the risk of the cancer coming back (recurrence). Hormonal therapy taken after surgery is called adjuvant hormonal therapy.

Scientists analyzed the results of seven studies looking at the benefits and risks of both types of adjuvant hormonal therapy. The analysis suggests that taking tamoxifen for several years and then switching to an aromatase inhibitor might be better than taking only tamoxifen or only an aromatase inhibitor for 5 years to reduce recurrence risk and improve overall survival. The research was published online on Aug. 29, 2011 by the Journal of the National Cancer Institute.

The aromatase inhibitors are:

  • Arimidex (chemical name: anastrozole)
  • Aromasin (chemical name: exemestane)
  • Femara (chemical name: letrozole)

A woman usually takes the same hormonal therapy medicine for all 5 years (monotherapy). Taking tamoxifen for 2 or 3 years and then switching to an aromatase inhibitor for another 2 or 3 years, until hormonal therapy has been taken for a total of 5 years (sequential therapy), is less common.

Taking an aromatase inhibitor for all 5 years is more common today than taking tamoxifen for all 5 years. A number of studies have shown that an aromatase inhibitor lowers the risk of recurrence more than tamoxifen.

Still, overall survival -- being alive whether or not breast cancer comes back -- isn't better with 5 years of an aromatase inhibitor compared to 5 years of tamoxifen. Some research suggests that overall survival may actually be worse with 5 years of an aromatase inhibitor compared to 5 years of tamoxifen.

By analyzing the results of the seven earlier studies, which included more than 30,000 women, the researchers found that:

  • Five years of an aromatase inhibitor is somewhat better than 5 years of tamoxifen for reducing recurrence risk in postmenopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer -- about 20% better overall.
  • Compared to 5 years of tamoxifen, 5 years of an aromatase inhibitor is linked to an 11% increase in the likelihood of dying without breast cancer coming back.
    • It's important to know that this increase wasn't statistically significant, which means that it could have been due to chance and not because of the difference in treatment.
  • Tamoxifen for 2 to 3 years followed by an aromatase inhibitor for 2 or 3 years can reduce recurrence risk about the same as taking an aromatase inhibitor for 5 years.
  • Tamoxifen for 2 to 3 years followed by an aromatase inhibitor for 2 or 3 years offers about the same overall survival as taking tamoxifen for 5 years and better overall survival than taking an aromatase inhibitor for 5 years.
  • The risk of heart problems is low with either type of hormonal therapy (under 5%); still, the risk of heart problems was 26% higher in women taking an aromatase inhibitor.
    • Women who took tamoxifen for 2 to 3 years and then an aromatase inhibitor for 2 or 3 more years had the same risk of heart problems as women who took 5 years of tamoxifen.
  • In rare cases, both tamoxifen and the aromatase inhibitors can lead to dangerous blood clots. This risk is higher with tamoxifen and lower with an aromatase inhibitor.

The possible link to worse overall survival with 5 years of an aromatase inhibitor compared to 5 years of tamoxifen -- even though recurrence risk is lower with an aromatase inhibitor -- may be due to more health problems associated with aromatase inhibitors compared to tamoxifen.

Both tamoxifen and the aromatase inhibitors have been linked to a small risk of uterine cancer. This risk is higher with tamoxifen and lower with an aromatase inhibitor.

The aromatase inhibitors can weaken bones and make women more likely to break a bone, though this is uncommon. Tamoxifen actually can strengthen bones. This study found that broken bones due to hormonal therapy were 47% more likely in women who got 5 years of an aromatase inhibitor compared to women who got 5 years of tamoxifen.

Research also has shown that hot flashes and night sweats -- called vasomotor symptoms -- are side effects of both tamoxifen and the aromatase inhibitors, though they're more common with tamoxifen. Joint pain is a more common side effect of the aromatase inhibitors.

If you're a postmenopausal woman diagnosed with hormone-receptor-positive, early-stage breast cancer, keep two things in mind when you and your doctor are deciding on an adjuvant hormonal therapy plan:

  • Every woman responds differently to treatment. What works for someone else may not work for you and what works for you may not work for someone else.
  • Your treatment plan isn't written in stone. You can always switch medicines if another treatment has greater benefits and/or fewer side effects.

Ask your doctor about the benefits and risks of aromatase inhibitors and tamoxifen for your unique situation, as well as the pros and cons of monotherapy compared to sequential therapy. Based on this study, sequential hormonal therapy (tamoxifen for 2 to 3 years followed by an aromatase inhibitor) may be a good choice for many women. Tamoxifen monotherapy or sequential hormonal therapy (starting with tamoxifen) may make more sense than aromatase inhibitor monotherapy if you have heart problems or are at high risk for heart problems.

Together, you and your doctor can decide on a treatment plan that's best for YOU.

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