Austrian Breast & Colorectal Cancer Study Group

Science from the heart of Europe

In 2006, the largest ABCSG study started including 49 centers in Austria and 5 in Sweden. A total of 3,425 patients participated, and in August 2013 the last patient was enrolled in the study. The study investigated whether the antibody drug denosumab reduces the therapy-induced risk of osteoporosis in breast cancer patients undergoing aromatase inhibitor therapy. On March 26, 2014, the first milestone PADCD (Primary Analysis Data Cut-Off Date) was reached with 247 clinical fractures – the results are now available and are surprisingly clear. The therapy-induced risk of osteoporosis can be reduced by 50 %! Administration of 60 mg denosumab subcutaneously twice a year halved clinical fractures, and also increased bone density in the spine by 10 percent, in the hip by about 8 percent, and in the femoral neck by 6 percent – without additional toxicities. These long-awaited data were presented in 2015 at the American Society of Clinical Oncology Annual Meeting (ASCO, May 29-June 2) in Chicago and published in the renowned journal „The Lancet“.

Three years later, in 2018, the results of the secondary study objective, disease-free survival, were also available. After an average of 72.6 months follow-up, these results were statistically significant as well, and the risk of relapse was reduced by approximately 18 % by the addition of denosumab. Of the patients who received additional denosumab, 89.2 % (versus 87.3 %) were disease-free at five years and 80.6 % (versus 77.5 %) at eight years. These considerable differences are particularly noteworthy given that prospect of recovery and survival in patients with this type of breast cancer are generally quite high. These data were presented on June 4, 2018, by Prof. Dr. Michael Gnant at the American Society of Clinical Oncology Annual Meeting (ASCO, June 1-5) in Chicago.

ABCSG has long focused its clinical research on innovative neoadjuvant therapies. The first successes became apparent in 2004, when the positive effect of neoadjuvant therapy was demonstrated in ABCSG 14: Doubling the number of chemotherapy cycles before surgery from 3 to 6 resulted in significant improvements. Pathological complete response (pCR), according to which previously existing tumor manifestations were no longer detectable, increased from 7 to 18 %.

These investigations were continued in study 24, which included 536 patients in Austria. According to this study, the proportion of patients with pCR increased to 24 % in the epirubicin + docetaxel + capecitabine group. This is 50 % more than in patients treated with the standard therapy epirubicin + docetaxel, where in 16 % of patients living cancer cells were no longer detected.

More recently, it was detected that this bisphosphonate increases the prospects of preventing recurrences in women with early breast cancer – i.e., it also has an antitumor effect. Compared to endocrine therapy alone, the prospects for reducing the risk of recurrence improve and survival increases dramatically: more than 98 % of the participants in study 12 were still alive 5 years after diagnosis, even without adjuvant chemotherapy.

This result led to considerable international attention and was one of the scientific highlights at ASCO 2008, as well as in 2010 and 2011. The renowned journal “The Lancet Oncology” also published the 62-month follow-up data of the study in its June 2011 issue.

The 84-month data have since confirmed these results: The probability of recurrence can be reduced by 28 % with zoledronate, and the overall survival of patients improves by around 36 %.

The second study result, presented in San Antonio, is also of great importance to female cancer patients. Many suffered from osteoporosis, a side effect of successful cancer treatment. ABCSG succeeded in proving that the addition of the bisphosphonate zoledronic acid to standard therapy can prevent this effect and thus significantly reduces the risk of bone fractures.

Two further ABCSG research results were presented at the Breast Cancer Symposium in San Antonio/Texas (SABCS) 2008, one of the most important meeting points of the international elite of cancer researchers, which have since attracted worldwide attention.

Firstly, the new treatment concept for hormone receptor-positive women after surgery. They now receive 2 years of the antiestrogen tamoxifen, which was already used for treatment, and subsequently 3 years of the aromatase inhibitor anastrozole. This “switch therapy” reduces the risk of developing new tumors by 40 %!

The aim of the study was to investigate whether prolonging therapy by a total of 8 years after surgery could increase patients’ chances of cancer survival.

The results were clear: the women benefited from prolonged endocrine therapy with the aromatase inhibitor to an unexpectedly high extent. As a result, the recurrence of breast cancer was reduced by 36 %.

The major breakthrough for ABCSG was the realization that the chances of breast cancer survival prior to menopause increase significantly if a combined endocrine therapy is administered after surgical intervention instead of the classic chemotherapy. The ABCSG 5 study gained international recognition when it was published in 2002; it was decisively taken into account when defining the “International Guidelines for Adjuvant Therapy of Primary Breast Carcinoma.”

This was the first major success of the Austrian study group and, above all, a success for the patients, who have since benefited from an endocrine therapy with considerably fewer side effects.