De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

The reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world. emtansine, pertuzumab to second-line chemotherapy in patients not treated with yielded clinical benefit In the PERTAIN trial, pertuzumab to first-line trastuzumab and therapy improved free benefit for chemotherapy in palliation of metastatic addition of veliparib to carboplatin and paclitaxel meaningfully outcomes in BRCA associated breast Preliminary data from the Olympia D trial suggest that olaparib is a more effective treatment of BRCA -associated advanced breast cancer than non-platinum options. PI3K mutations are common in advanced breast cancer. Randomized trials are evaluating the addition of PI3K inhibitors to endocrine therapy. These agents vary in their targeting of PI3K isoforms, and the trials differ in their inclusion and assessment of tumors by PI3K mutation status. To date, there are no clinically compelling outcomes from these studies There may be more activity with more alpha-selective agents in tumors with PI3K mutations.