Aromatase inhibitors as upfront therapy for early-stage breast cancer

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In upfront therapy after breast surgery, aromatase inhibitors are taken for five years. The aromatase inhibitors anastrozole and letrozole have been approved for use in upfront therapy in Germany.

In 2016, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of aromatase inhibitors used as upfront therapy for women with early-stage breast cancer.

The Institute analyzed how aromatase inhibitors as upfront therapy compared to standard treatments such as tamoxifen. The Institute found two relevant studies in this area. One study involving 6,241 women compared anastrozole with tamoxifen. The other study compared letrozole with tamoxifen and analyzed the data from 4,922 women. The main results are described below.

What are the advantages of aromatase inhibitors as upfront therapy?

  • Life expectancy: From the study results it can be concluded that aromatase inhibitors can prolong life more than tamoxifen can: About 23 out of 100 women who took tamoxifen had passed away after ten years, compared to about 21 out of 100 women who took aromatase inhibitors.
  • Life without relapses: Aromatase inhibitors can prevent relapses: About 30 out of 100 women who took tamoxifen had a relapse or passed away within about ten years, compared to about 26 out of 100 women who took aromatase inhibitors.
  • Severe side effects: Serious side effects are less common during treatment with aromatase inhibitors than during treatment with tamoxifen. About 30 out of 100 women experienced severe side effects while taking tamoxifen, compared to about 28 women who were taking an aromatase inhibitor.
  • Treatment stopped due to side effects: One study found that women who take anastrozole are less likely to stop their treatment: About 14 out of 100 women who took tamoxifen stopped the treatment due to side effects, compared to about 11 out of 100 women who took anastrozole. No such difference was found when letrozole was compared with tamoxifen.
  • Severe thrombosis: In severe thrombosis, a blood clot blocks a blood vessel, which can cause deep vein thrombosis (DVT) or pulmonary embolism. The studies showed that this side effect was less common in women who took aromatase inhibitors. For instance, during treatment with tamoxifen about 2 to 3 out of 100 women had severe thrombosis of the leg veins. This happened in about 1 to 2 out of 100 women who took aromatase inhibitors.

What are the disadvantages of aromatase inhibitors as upfront therapy?

  • Bone fractures: The studies showed that bone fractures are more common during treatment with aromatase inhibitors than during treatment with tamoxifen: About 7 out of 100 women who took tamoxifen had bone fractures, compared to about 10 out of 100 women who took aromatase inhibitors.

No difference

  • Strokes and bleeding in the brain: The studies found no differences between treatments in terms of severe cerebrovascular events such as strokes and bleeding in the brain.
  • Severe cardiovascular disease: Here too, there was no difference between aromatase inhibitors and the standard treatment.

What remains unanswered?

  • Symptoms: The studies contain no suitable data about the effect of aromatase inhibitors on the symptoms caused by breast cancer.
  • Quality of life: Most of the studies didn't provide any suitable data about the effect of aromatase inhibitors on the women's quality of life. One study found no difference here between anastrozole and tamoxifen after two years.
  • Hormonal diseases: Treatment of breast cancer can cause a number of hormonal side effects such as thyroid problems. Most of the studies didn't provide any suitable data about the effect of aromatase inhibitors on severe hormonal diseases. One study found no difference here between anastrozole and tamoxifen after two years.
  • Malignant new growths: Treatments for breast cancer may also cause a new tumor to grow. The studies contain no suitable data about the effect of aromatase inhibitors on malignant new growths in women.