Zoledronic acid reduces spread of cancer cells in women undergoing chemotherapy for locally advanced breast cancer

Zoledronic acid reduces spread of cancer cells in women undergoing chemotherapy for locally advanced breast cancer

An article published Online First in The Lancet Oncology reports that zoledronic acid, which is a bone strengthening drug, when given together with chemotherapy might decrease the spread of cancer in women with locally advanced breast cancer. It reduces the likelihood of tumour cells growing in bone marrow and spreading to other parts of the body.

Nearly 25 percent of breast cancers spread to the bone first. Bone marrow is a safe haven for disseminated tumour cells (DTCs). The cells are released from the primary tumour and this is where they adapt and spread to other organs. Research has shown that women with DTCs in their bone marrow are at increased risk of developing distant disease and death.

Earlier studies have revealed that chemotherapy increases rates of bone turnover. This releases bone-derived growth factors which could then promote tumour growth in women with breast cancer. Zoledronic acid is a bisphosphate that reduces bone loss by slowing down the activity of cells that destroy bone. There is indication that it has the potential to alter the microenvironment making it less favourable for cancer cells. This could result in a decrease in metastatic disease.

Rebecca Aft from Washington University School of Medicine, USA, and colleagues carried out a randomised phase 2 trial. They examined the effects of zoledronic acid on DTCs in women undergoing chemotherapy for locally advanced breast cancer.

A total of 120 women were randomly assigned to 4 mg zoledronic acid every 3 weeks for one year starting with their first dose of chemotherapy, or to chemotherapy alone with no zoledronic acid. Bone marrow samples were taken at the start of the study and again at three months and one year after treatment. At the start of the study, 45.7 percent of patients had detectable tumour cells in their bone marrow.

Results indicated that women who were given zoledronic acid had fewer detectable tumour cells after three months of treatment compared to women who received chemotherapy alone (30 percent compared to 47 percent).

Findings showed that at three months, women who started the study with no tumour cells in their bone marrow remained free of tumour cells in:

• 87 percent in the zoledronic acid group

• 60 percent in the group who received chemotherapy alone

One year after treatment, there was no significant difference in the number of patients with detectable tumour cells in their bone marrow between the two groups (40 percent for zoledronic acid compared to 33 percent for chemotherapy alone).

Furthermore, zoledronic acid was effective at preventing treatment-related bone loss at one year. In the women with mild osteopenia (which is low bone mineral density) at the start of the study, 44 percent had normal bone-mineral density after one year of treatment with zoledronic acid. There were significant decreases in bone-turnover markers at three months and one year after treatment.

There were no differences in side effects between the two treatment groups and zoledronic acid was generally well tolerated. The most common serious adverse events were infection and thrombosis. One case of osteonecrosis of the jaw was reported in the zoledronic acid group.

The authors write: "Zoledronic acid has antimetastatic properties within the bone marrow and systemically."

They add: "Chemotherapy leads to increased bone turnover and the release of growth factors, providing a favourable environment for DTCs, and that this effect is abrogated by treatment with bisphosphonates."

The authors recommend additional studies to address the optimum timing of administration, dose, and target population of bisphosphonate treatment in patients with breast cancer.

"Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label,randomised, phase 2 trial"

Rebecca Aft, Michael Naughton, Kathryn Trinkaus, Mark Watson, Lourdes Ylagan, Mariana Chavez-MacGregor, Jing Zhai, Sacha Kuo,William Shannon, Kathryn Diemer, Virginia Herrmann, Jill Dietz, Amjad Ali, Matthew Ellis, Peter Weiss, Timothy Eberlein, Cynthia Ma,Paula M Fracasso, Imran Zoberi, Marie Taylor, William Gillanders, Timothy Pluard, Joanne Mortimer, Katherine Weilbaecher

DOI: 10.1016/S1470-2045(10)70054-1

The Lancet Oncology

Adjuvant Zoledronic Acid Reduces Breast Cancer Deaths (Video Medical And Professional 2020).

Section Issues On Medicine: Women health