Biopsy-Guided Pathological Response Assessment in Breast Cancer is Insufficient: Additional Pathology Findings of the MICRA Trial

Abstract

Background Neoadjuvant systemic treatment (NST) leads to pathologic complete response (pCR) in 10–89% of breast cancer patients depending on subtype. The added value of surgery is uncertain in patients who reach pCR; however, current imaging and biopsy techniques aiming to predict pCR are not accurate enough. This study aims to quantify the residual disease remaining after NST in patients with a favorable response on MRI and residual disease missed with biopsies. Methods In the MICRA trial, patients with a favorable response to NST on MRI underwent ultrasound-guided post-NST 14G biopsies followed by surgery. We analyzed pathology reports of the biopsies and the surgical specimens. Primary outcome was the extent of residual invasive disease among molecular subtypes, and secondary outcome was the extent of missed residual invasive disease. Results We included 167 patients. Surgical specimen showed residual invasive disease in 69 (41%) patients. The median size of residual invasive disease was 18 mm (interquartile range [IQR] 12–30) in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) patients, 8 mm (IQR 3–15) in HR+/HER2-positive (HER2+) patients, 4 mm (IQR 2–9) in HR-negative (HR−)/HER2+ patients, and 5 mm (IQR 2–11) in triple-negative (TN) patients. Residual invasive disease was missed in all subtypes varying from 4 to 7 mm. Conclusion Although the extent of residual invasive disease is small in TN and HER2+ subtypes, substantial residual invasive disease is left behind in all subtypes with 14G biopsies. This may hamper local control and limits adjuvant systemic treatment options. Therefore, surgical excision remains obligatory until accuracy of imaging and biopsy techniques improve.

Triple-induction treatment for locally advanced non-small cell lung cancer: a case report of pathological complete response

“…Pathological response currently holds the highest predictive value for event-free survival when compared to the radiographic response or circulating tumor DNA clearance, and may ultimately guide subsequent adjuvant therapy in the perioperative setting [ 12 ]. A biopsy-guided pathological response assessment has been recently investigated in other cancer entities and is an insufficient predictor of pCR [ 13 , 14 ]. In our case, the good functional reserve and the reduced perfusion of the left lung in the V/Q scan indicated that a left pneumonectomy was safe and feasible.…”

ASO Author Reflections: Biopsy Guided Pathological Response Assessment in Breast Cancer is Insufficient: Additional Pathology Findings of the MICRA Trial

“…Our pathology analysis of the MICRA study shows that limited but relevant residual invasive disease was missed in patients with TN or HER2-postive breast cancer when surgery was omitted. 19 Therefore, it is time to consider alternative de-escalation strategies, such as omission of radiotherapy instead of surgery. The DESCARTES trial (De-ESCAlating RadioTherapy in breast cancer patients with pathologic complete response to neoadjuvant systemic therapy, NCT05416164) aims to show the safety of omission of radiation treatment in cT1–2N0 patients achieving pCR after NST, detected with surgery.…”