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Integrating poly(ADP-ribose) polymerase (PARP) inhibitors in the treatment of early breast cancer

Garber, Haven R.a; Litton, Jennifer K.b

doi: 10.1097/CCO.0000000000000516
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Purpose of review Poly(ADP-ribose) polymerase (PARP) inhibitors were recently approved for the treatment of patients with BRCA1 or BRCA2 germline pathogenic variants and metastatic breast cancer. PARP inhibitors have also demonstrated activity in early stage breast cancer, and this review discusses completed and ongoing trials of PARP inhibitors in the neoadjuvant and adjuvant setting.

Recent findings A recent phase II trial of neoadjuvant talazoparib monotherapy in patients with BRCA1 or BRCA2 germline pathogenic variants and early stage breast cancer demonstrated a pathological complete response in 10/19 (53%) patients. Previous trials of PARP inhibition in early stage breast cancer included the I-SPY-2 and BrighTNess trials, which ultimately failed to show a benefit for adding the PARP inhibitor veliparib to standard neoadjuvant chemotherapy in patients with triple-negative breast cancer. Investigators are building on these results by designing novel clinical trials for patients with BRCA1/2-deficient tumors and/or triple-negative breast cancer.

Summary The OlympiAD and EMBRACA trials that led to the recent approval of PARP inhibitors for metastatic breast cancer patients with BRCA1/2 germline pathogenic variants are practice changing. Investigators are now working to translate this success into the early breast cancer setting where ongoing trials incorporate new dosing schedules, PARP inhibitor monotherapy, and novel PARP combinations.

aDivision of Cancer Medicine – Hematology/Oncology Fellowship Program

bDivision of Cancer Medicine, Department of Breast Medical Oncology, Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, Houston, USA

Correspondence to Jennifer K. Litton, MD, Associate Professor, Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1354, Houston, TX 77030, USA. Tel: +1 713 792 2817; e-mail: jlitton@mdanderson.org

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