Comparative Study of Neoadjuvant Chemotherapy With and Without Zometa for Management of Locally Advanced Breast Cancers
Status:
Completed
Trial end date:
2014-04-01
Target enrollment:
Participant gender:
Summary
Breast cancer is the leading female cancer by a very wide margin in France. Despite
widespread breast cancer screening, many cases of breast cancer are discovered at a locally
advanced stage. The tumoral consequences of a cancer size greater than 3 cm are: increased
risk of metastasis and death and, most often, impossibility of performing breast-conserving
surgery (a mastectomy is usually advisable in case of a first surgical procedure). It is
increasingly recommended to treat locally advanced breast cancers with neoadjuvant
chemotherapy. Very numerous studies have shown that by proceeding that way, the oncologic
prognosis was not harmed and, on the contrary, it was possible to obtain sufficient tumor
response to allow breast-conserving treatment in more than 60% of cases.
The use of zoledronic acid (Zometa) has an established place in the management of
malignancies with a predilection for skeletal involvement (in particular metastasis).
Although the main target of biphosphonates is the osteoclast, there is also preclinical data
indicating that biphosphonates can have effects on cells other than osteoclasts, including
tumor cells. Anti-tumor activity including inhibition of tumor cell growth and induction of
tumor cell apoptosis, inhibition of tumor cell adhesion and invasion, and anti-angiogenic
effects have been demonstrated. In addition several in vitro studies have shown that Zometa
causes synergistic induction of breast cancer cell apoptosis when combined with clinically
relevant concentrations of chemotherapy drugs such as paclitaxel and doxorubicin. Therefore
testing of combinations of biphosphonates with these agents in breast cancer is of
significant interest.
In the context of locally advanced breast cancers, the combination of a bisphosphonate with
neoadjuvant chemotherapy appears to have an important potential: preventing possible bone
metastases, but also possibly amplifying the efficacy of the chemotherapy's tumoricidal
activity, both on the primary tumor and on potential metastatic localizations.
So it appears that, the use of bisphosphonates in a neoadjuvant situation presents a
potentially favorable benefit-risk ratio. That is why we are proposing to perform a
prospective randomized multicenter comparative study to evaluate 2 systemic neoadjuvant
treatments, one with Zometa and the other without Zometa, in patients with locally advanced
breast cancer. Zometa will be administered according to the usual administration procedure:
one infusion every 3 weeks.
The therapeutic response will be evaluated by studying the different biological markers
(circulating blood and bone marrow tumor cells, serum cell apoptosis and neoangiogenesis
markers, bone resorption markers, etc.), but also by analyzing clinical, radiologic, and
histologic response and by breast conservation rates. The impact of other factors that may
affect therapeutic response will be taken into account: aggressivity of the tumor, presence
or absence of tumor receptors, tumor stage, etc.
The purpose of the study is to show a marked benefit of treatment with Zometa in managing
locally advanced breast cancers with synergistic action of the neoadjuvant chemotherapy and
improvement in the laboratory parameters of tumor aggressivity. These markers will be used as
surrogate markers of long term outcome.