All Bisphophonates Reduce Recurrence Risk the Same Amount

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Bisphosphonates are medicines used to prevent or treat osteoporosis. They do this by limiting the activity of certain bone cells, called osteoclasts, which help cause the bone weakening and breakdown that leads to osteoporosis.

Bisphosphonates also may help stop breast cancer from spreading to the bones by making it harder for breast cancer cells to grow in bones. Doctors have wondered if bisphosphonates would help reduce the risk of recurrence (the cancer coming back) in women diagnosed with early-stage breast cancer. The bisphosphonates studied to reduce breast cancer recurrence risk are:

  • Reclast (chemical name: zoledronic acid)
  • Zometa (chemical name: zoledronic acid)
  • Boniva (chemical name: ibandronate)
  • Bonefos (chemical name: clodronate)

Reclast and Zometa are both zoledronic acid, but are different formulations.

While early research results were mixed on whether bisphosphonates help reduce recurrence risk, a study presented at the 2013 San Antonio Breast Cancer Symposium suggested that bisphosphonates do reduce the risk of recurrence, but only in postmenopausal women or women who have been made postmenopausal through ovarian suppression.

Doctors then wondered if different bisphosphonates offered different levels of recurrence risk reduction.

A study suggests that all the bisphosphonates offer the same benefits.

The research was presented at the American Society of Clinical Oncology Annual Meeting on June 1, 2015. Read the abstract of “Phase III trial of bisphosphonates as adjuvant therapy in primary breast cancer: SWOG/Alliance/ECOG-ACRIN/NCIC Clinical Trials Group/NRG Oncology study S0307.”

The study involved 6,097 women diagnosed with early-stage breast cancer who were getting systemic therapy after breast cancer surgery. Unlike local therapies, which focus on the area or areas where the cancer was, systemic therapies treat cancer cells throughout the body. Chemotherapy, hormonal therapy, and targeted therapy are systemic therapies. About 50% of the women were postmenopausal or older than 50. Nearly 80% of the breast cancers were hormone-receptor-positive, 17% were HER2-positive, and 16% were hormone-receptor-negative and HER2-negative (triple negative).

The women were randomly assigned to also get one of three bisphosphonates for 3 years:

  • Bonefos
  • Boniva
  • zoledronic acid -- it’s not clear if the zoledronic acid was Zometa or Reclast

Bonefos and Boniva are pills taken by mouth. The zoledronic acid is given as an IV infusion through a needle inserted in a vein.

The researchers wanted to see if one of the bisphosphonates would improve disease-free survival more than the others. Disease-free survival is how long the women lived without the cancer coming back.

After about 5.4 years of follow-up, the researchers found that 88% of the women were living and had not had a recurrence. This rate was the same no matter which bisphosphonate the women got.

When the researchers looked at the women by the type of breast cancer they had been diagnosed with, they found the disease-free survival rates varied slightly by cancer type. Still, when looking at individual cancer types, all the bisphosphonates offered the same benefits.

The 5-year overall survival rate was 93%. This means that after 5 years, 93% of the women were alive, whether or not the cancer had recurred. There was no difference in overall survival between the different bisphosphonate groups.

The rate of serious side effects was the same among the three treatment groups. Still, women who were treated with zoledronic acid had a higher risk of osteonecrosis of the jaw compared to women who were treated with Bonefos or Boniva. Osteonecrosis of the jaw is a rare but serious side effect in which the cells in the jawbone start to die. Researchers think that osteonecrosis of the jaw may develop because bisphosphonates stop the body from repairing microscopic damage to the jawbone that can happen during routine dental procedures or from every day wear and tear. But it's still not clear why this happens in some people and not in others.

While these results are promising, more research is needed before doctors know exactly how bisphosphonates reduce recurrence risk, as well as which groups of women might benefit from taking a bisphosphonate to reduce risk.

Stay tuned to Breastcancer.org for the latest news on how bisphosphonates might be used against breast cancer.



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