Systemic treatment of patients with early breast cancer: recent updates and state of the art

Abstract

This review is focused on trials generating results that potentially impacted clinical practice since the 2017 St. Gallen Consensus; the most impactful trial was KATHERINE, which revealed a 11.3% absolute iDFS improvement with T-DM1 (compared to trastuzumab) in HER2-positive breast cancer patients who presented invasive residual disease following neoadjuvant treatment. These results, if reinforced by a subsequent overall survival benefit, will consolidate neoadjuvant treatment as the standard-of-care for most HER2-positive breast cancer patients. The addition of pertuzumab to adjuvant trastuzumab (APHINITY) or extending anti-HER2 therapy with 1 year of neratinib (ExteNET) also improved outcomes, but in a more modest way. In triple-negative early breast cancer patients presenting invasive residual disease after neoadjuvant chemotherapy, the CREATE-X trial demonstrated the benefit of post-neoadjuvant capecitabine. In patients with luminal tumours, updated results of the SOFT/TEXT trials confirmed the benefit of aromatase inhibitors plus ovarian suppression in highrisk premenopausal patients, and the 12-year results of the BIG1-98 trial demonstrated a sustained trend in favour of letrozole compared to tamoxifen in the adjuvant treatment of postmenopausal patients. The TAILOR-X study showed that, overall, patients with an intermediate recurrence risk score (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) in the OncotypeDX 21gene assay did not benefit from adjuvant chemotherapy. A meta-analysis performed by the EBCTCG demonstrated that extended adjuvant aromatase inhibitors modestly reduced breast cancer recurrence risks, with a more pronounced benefit in patients previously treated with tamoxifen. Finally, an EBCTCG meta-analysis including patients with all breast cancer subtypes showed that dose-dense chemotherapy improved survival when compared to conventionally-timed chemotherapy.

Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway

“…For ER + breast cancer, primary therapy is endocrine treatment. There are reports showing that antiestrogen treatment can dramatically improve the treatment outcome and reduce the recurrence risk for patients with ER + breast cancer 2 . Tamoxifen (TAM) is the most widely used nonsteroidal and antiestrogen agent for ERα + patients 3 .…”

Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up

“…Today, HER2-directed therapies are considered standard of care in the advanced-and early-disease settings. [1][2][3] Trastuzumab when added to chemotherapy has shown improvement in overall survival (OS) in patients with advanced and early HER2-positive BC. [4][5][6][7] Interest in dual HER2 blockade grew rapidly in view of the improvement in OS seen in the advanced disease and improvements in pathological complete response rates in several neoadjuvant trials.…”

Prognostic Significance of BIRC5/Survivin in Breast Cancer: Results from Three Independent Cohorts

“…This meant that we compared clinical outcomes in the datasets, which enrolled and followed BC patients separated by 2–3–4 decades. The survival curves of these different cohorts justify the current progress in BC diagnosis and treatment [ 44 , 45 ]. Despite being diagnosed in different decades and most likely receiving different treatment regimens, the patients with high BIRC5/survivin tended to show an adverse survival outcome.…”