The osteoporosis drug zoledronic
acid boosts disease-free breast cancer survival by 36%
when taken with either tamoxifen or anastrozole. That's
one of the key results of the Austrian ABCSG-12 trial
presented at the annual meeting of the American Society
of Clinical Oncology in Chicago on May 31.
The researchers found no difference
between tamoxifen and anastrozole when given on their
own, but addition of the bisphosphonate significantly
improved outcomes. The study included more than 1,800
premenopausal women with stage I or II breast cancer.
After resection of their tumours — all endocrine-positive
— the patients received goserelin therapy for ovarian
suppression combined with either tamoxifen or anastrozole;
the study group also received zoledronic acid. Treatment
duration was three years, with a median follow-up of
five years. Though some women underwent radiation therapy
around the surgery, they didn't get any chemo afterwards.
BONE
BOON
It isn't yet well understood how the osteoporosis drug
affects tumour growth and metastasis, but the study
authors observed a beneficial effect across all categories
of disease progression. Patients receiving zoledronic
acid showed a reduction in local regional recurrence,
in distant metastasis — including, but not limited
to, bone metastasis — as well as in contralateral
breast cancer. The drug, which inhibits the breakdown
of bone, is currently approved in Canada for osteoporosis
and Paget's disease; it's also regularly given to breast
cancer patients with bone metastases.
"It's been shown in pre-clinical
studies that zoledronic acid can interfere with tumour
cell adhesion, inhibit tumour cell growth, induce tumour
cell apoptosis, but also inhibit angiogenesis and stimulate
the immune response," explained lead author Dr Michael
Gnant. He speculates that the combination of endocrine
treatment with the bisphosphonate creates a tumour-hostile
environment, resulting in benefits not only in the incidence
of bone metastasis, but across the board.
SAFE
AND SOUND
With respect to safety of the treatment combo, the researchers
found that the side effect profile was well within the
expected limits. Osteonecrosis of the jaw (ONJ) is one
of the main concerns with zoledronic acid, which is
given intravenously once a year when used for osteoporosis.
In the ABCSG-12 trial, 4mg of the drug were injected
once every six months. "I'm glad to report to you that
we have not a single confirmed ONJ case in this trial,"
said Dr Gnant.
Indeed, he could barely contain
his excitement throughout his presentation, proposing
physicians consider adjuvant zoledronic acid for all
their premenopausal breast cancer patients.
Not so fast, says Dr Martine Piccart-Gebhart,
assistant professor of oncology at the University of
Brussels, commenting on the study. She called this "an
important trial" but insisted that it's "not yet a practice-changing
trial." Before making recommendations, the best dosage
and schedule for treatment with the bisphosphonate need
to be settled, she said. Results from other trials investigating
adjuvant treatment with zoledronic acid are expected
this summer.
OVERALL
SURVIVAL
In a nice twist, the researchers observed such fantastic
survival rates in this study that teasing out the effect
of the bisphosphonate on overall survival became tricky:
"The hazard ratio is 0.59 — that's about a 40%
reduction. But due to the fortunate low number of deaths
in this trial as of yet this is not statistically significant,"
explained a jubilant Dr Gnant during his presentation.
|
