M. Piccart-Gebhart MD, PhD

Lessons learned after two decades of international academic clinical research in breast cancer: 2019 JC Heuson Memorial Lecture

SUMMARY

The Breast International Group (BIG), founded in 1999, is the umbrella organisation harnessing the efforts and supporting the activities of its nearly 60 national and international cooperative group members worldwide. BIG’s collaborative research model provides academic leadership in industry-sponsored randomised clinical trials. Some of these trials have successfully led to the rapid registration of new anticancer drugs with a significant impact on breast cancer mortality, such as the HERA trial, which contributed to the registration of adjuvant trastuzumab in many countries around the world in less than four years. BIG also supports clinical trials sponsored by its academic member groups and facilitates collaboration between international researchers and the US cooperative groups: the SOFT and TEXT trials evaluating adjuvant endocrine therapies for 5,738 premenopausal women are an example of such a collaboration, which has helped clarify which women can be safely treated with tamoxifen and which women are best served by a combination of tamoxifen or an aromatase inhibitor with an LHRH agonist. BIG is most proud of its ambitious purely ‘academic’ initiatives: namely MINDACT and AURORA.

MINDACT, which was recently updated at a median follow-up of 8.7 years on its 6,693 enrolled patients, most of whom had hormone receptor positive/HER2 negative (HR+ HER2−) early breast cancer, continues to demonstrate the clinical utility of a low risk 70 gene signature for foregoing adjuvant chemotherapy in the presence of a high clinical risk (and no more than three positive nodes) in women older than 50 years. In younger women, a clinically relevant chemotherapy benefit of about 5% has emerged and should be part of informed shared decision-making. AURORA is an ongoing European effort at elucidating the clonal evolution of breast cancer towards the development of lethal metastasis: with close to 1,000 women with metastatic breast cancer already enrolled, it aims at the integration of multiple genomic analyses with high quality clinical data, longitudinal sampling and a biobank. Its impact could be improved treatment strategies and personalisation in the years to come.

(BELG J MED ONCOL 2020;14(7):327-32)

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Treatment options in patients with early breast cancer and BRCA-mutations or family history of cancer

Women diagnosed with BRCA1/2 mutation positive breast cancer have an increased lifetime risk of contralateral breast cancer and ovarian cancer. They benefit from risk-reducing surgical strategies such as mastectomy and salpingo-oophorectomy. For patients with BRCA mutations and hormone-receptor positive breast cancer, the option of combined bilateral annexectomy and hormonal therapy with Aromatase Inhibitor can be discussed with high-risk patients. For triple negative breast cancer with BRCA mutation, there is some evidence that adding platinum-agents in the neoadjuvant setting improves the pathologic complete response. Lastly, ongoing clinical trials testing the efficacy of poly (ADP-ribose) polymerase inhibitor therapy in patients with BRCA1/2 mutations will be determinant for the future guideline recommendations in determining best treatment options for these patients.

(BELG J MED ONCOL 2018;12(5):239–246)

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