Abstract P5-16-30: Feasibility trial for identification of patients for eliminating breast cancer surgery following neoadjuvant systemic therapy

Abstract

Background: Contemporary improved neoadjuvant systemic therapy (NST) for breast cancer may result in a pathologic complete response (pCR) in up to 60% of patients (pts) yet imaging alone has a poor negative predictive value to determine which pts might be spared surgery. This study was designed to evaluate the hypothesis that percutaneous image guided biopsy after NST can accurately identify patients who may forgo surgery. Methods: Prospective single-center IRB approved study of 34 pts with clinical T1-3 N0-3 triple-negative (TN, n=23) or HER2-positive (n=11) invasive ductal cancer who received standard NST and consented for ultrasound/mammography guided vacuum-assisted core biopsy (VACB) and fine-needle aspiration (FNA) biopsy prior to standard surgery. Main outcome measures included accuracy, false-negative rate (FNR), and negative predictive value of image guided biopsy in predicting residual disease after NST. Breast pCR was defined as no residual DCIS or invasive disease. Final biopsy showing atypia and/or suspicion of residual disease was recorded as positive. Results: Median initial maximum tumor size based on imaging and physical exam was 3 cm (1.2-7 cm) and 47.1% had FNA/core biopsy proved nodal metastases. Final median maximum residual tumor size after NST was 0.9 cm (0-4.2 cm) with 94.1% having no palpable abnormality. Median number of VACB (9G) removed following NST was 10 (4-14) and was performed by stereotactic (67.6%) or ultrasound (32.4%) guidance. Overall, a breast pCR occurred in 18 (52.9%) of pts and breast pathologic response was concordant with nodal pathologic response in 33 (97%) of pts (1 pt with a breast pCR had 1/15 nodes with metastases). Overall, VACB combined with FNA following NST had a 100% (95% CI 89.7-100) accuracy, 0% FNR (95% CI 0-20.6), and 100% (95% CI 81.5-100) negative predictive value for determination of residual breast disease. Grade 1 adverse events which resolved from biopsy (bleeding, hematoma, bruising) occurred in 6 pts (17.6%). Conclusions: High rates of pCR among pts with TN/HER2-positive breast cancer receiving NST occur in a significant proportion of pts. The use of image guided VACB/FNA can identify pts after NST where significant residual disease is unlikely. Based on these results, an IRB approved clinical trial will shortly commence for pts with T1-2 TN/HER2-positive breast cancer with documented image guided biopsy proved pCR after NST to be followed by standard definitive whole-breast radiotherapy without surgery.Background: Contemporary improved neoadjuvant systemic therapy (NST) for breast cancer may result in a pathologic complete response (pCR) in up to 60% of patients (pts) yet imaging alone has a poor negative predictive value to determine which pts might be spared surgery. This study was designed to evaluate the hypothesis that percutaneous image guided biopsy after NST can accurately identify patients who may forgo surgery. Methods: Prospective single-center IRB approved study of 34 pts with clinical T1-3 N0-3 triple-negative (TN, n=23) or HER2-positive (n=11) invasive ductal cancer who received standard NST and consented for ultrasound/mammography guided vacuum-assisted core biopsy (VACB) and fine-needle aspiration (FNA) biopsy prior to standard surgery. Main outcome measures included accuracy, false-negative rate (FNR), and negative predictive value of image guided biopsy in predicting residual disease after NST. Breast pCR was defined as no residual DCIS or invasive disease. Final biopsy showing atypia and/or suspicion of residual disease was recorded as positive. Results: Median initial maximum tumor size based on imaging and physical exam was 3 cm (1.2-7 cm) and 47.1% had FNA/core biopsy proved nodal metastases. Final median maximum residual tumor size after NST was 0.9 cm (0-4.2 cm) with 94.1% having no palpable abnormality. Median number of VACB (9G) removed following NST was 10 (4-14) and was performed by stereotactic (67.6%) or ultrasound (32.4%) guidance. Overall, a breast pCR occurred in 18 (52.9%) of pts and breast pathologic response was concordant with nodal pathologic response in 33 (97%) of pts (1 pt with a breast pCR had 1/15 nodes with metastases). Overall, VACB combined with FNA following NST had a 100% (95% CI 89.7-100) accuracy, 0% FNR (95% CI 0-20.6), and 100% (95% CI 81.5-100) negative predictive value for determination of residual breast disease. Grade 1 adverse events which resolved from biopsy (bleeding, hematoma, bruising) occurred in 6 pts (17.6%). Conclusions: High rates of pCR among pts with TN/HER2-positive breast cancer receiving NST occur in a significant proportion of pts. The use of image guided VACB/FNA can identify pts after NST where significant residual disease is unlikely. Based on these results, an IRB approved clinical trial will shortly commence for pts with T1-2 TN/HER2-positive breast cancer with documented image guided biopsy proved pCR after NST to be followed by standard definitive whole-breast radiotherapy without surgery. Citation Format: Kuerer HM, Rauch GM, Krishnamurthy S, Adrada BE, Caudle AS, DeSnyder SM, Santiago L, Lucci A, Hobbs BP, Gilcrease M, Hwang R, Candelaria RP, Chavez Mac-Gregor M, Arribas E, Moseley T, Teshome M, Miggins MV, Smith BD, Valero V, Hunt KK, Yang WT. Feasibility trial for identification of patients for eliminating breast cancer surgery following neoadjuvant systemic therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-30.

Identification of Patients With Documented Pathologic Complete Response in the Breast After Neoadjuvant Chemotherapy for Omission of Axillary Surgery

“…Prior clinical studies that aimed to eliminate surgery in exceptional responders did not meet the threshold of success for the routine omission of surgery among these patients owing to the inability to reliably identify patients with a breast pCR. Outstanding initial results from the MD Anderson feasibility trial using extensive image-guided sampling of the tumor bed after NCT have provided an opportunity to test the hypothesis that surgery may be eliminated in many patients with a documented breast pCR.…”

“…Initial attempts at elimination of surgery among patients with a complete clinical response were unsuccessful, because imaging of the breast and lymph nodes had a poor negative predictive value for a pCR and therefore was associated with unacceptable local regional recurrence rates after radiotherapy alone . However, use of improved imaging techniques with extensive vacuum-assisted core biopsy and fine-needle aspiration (FNA) biopsy of the known tumor bed (with removal of the initially placed clip) has recently been shown to accurately identify patients with a pCR and in whom significant residual disease in the breast is unlikely . In the initial results of the MD Anderson feasibility clinical trial with 34 patients, the use of image-guided biopsy was associated with 100% accuracy and no false-negative findings for the determination of residual disease in the breast after NCT.…”

“…However, use of improved imaging techniques with extensive vacuum-assisted core biopsy and fine-needle aspiration (FNA) biopsy of the known tumor bed (with removal of the initially placed clip) has recently been shown to accurately identify patients with a pCR and in whom significant residual disease in the breast is unlikely . In the initial results of the MD Anderson feasibility clinical trial with 34 patients, the use of image-guided biopsy was associated with 100% accuracy and no false-negative findings for the determination of residual disease in the breast after NCT. Similar prospective, multicenter, cooperative group studies are planned or have been commenced by the NRG Oncology Group (formerly the National Surgical Adjuvant Breast and Bowel Project [NSABP], Radiation Therapy Oncology Group [RTOG], and Gynecologic Oncology Group [GOG]), the German Breast Group, and other national and international single centers …”

Nonoperative Management for Invasive Breast Cancer After Neoadjuvant Systemic Therapy: Conceptual Basis and Fundamental International Feasibility Clinical Trials

“…The accuracy of fine-needle aspiration (FNA) and vacuum-assisted core biopsy (VACB) was determined in assessing pCR (no invasive or in situ disease) following NST. 16 The sample size of 40 was determined to provide sufficient information to characterize the diagnostic properties of VACB assuming an estimated 90% sensitivity and specificity for VACB after NST. Forty patients with clinical T1-3N0-3 limited to TN or HER2-positive breast cancer receiving NST were enrolled.…”