Abstract P1-15-12: Axillary lymph node metastasis and HER2-receptor positivity significantly associate with recurrence and worse survival in breast cancer patients who achieved pathological complete response after neoadjuvant chemotherapy
Authors: Asaoka M , Narui K , Suganuma N , Chishima T , Yamada A , Kawai S , Uenaka N , Sato E , Katsuta E , Kawaguchi T , Takabe K , Ishikawa T 
Published: May 2019

Abstract
BACKGROUND
Neoadjuvant chemotherapy (NAC) has become a common practice in breast cancer care since it not only expands the opportunity for breast conservation surgery, but also allows in vivo assessment of individual cancer biology. Patients who achieved pathological complete response (pCR) after NAC are known to have significantly improved outcomes than those who did not. To date, there has been no large study of factors that associate with tumor recurrence after patients had pCR following NAC. To identify such factors, we examined a cohort of 394 patients.
METHODS
Patients diagnosed during 2007-16 with clinical stage I-III breast cancer who achieved pCR following NAC were identified from clinical records at four hospitals in urban Japan. Nearly 70% of patients received standard NAC regimen, which was a combination of anthracycline and taxane, with trastuzumab added as needed. pCR was defined as no pathological evidence of invasive cancer in the breast; residual ductal carcinoma in situ (DCIS) and residual axillary lymph node metastasis were included in this study. The median follow-up time was 63 months (range = 16-161 months). Outcomes were assessed by 5-year disease-free survival (DFS) and 5-year overall survival (OS).
RESULTS
Among the 394 patients with pCR, the breast cancer subtype was as follows: Luminal – 49 (12.4%), Luminal-HER2 – 97 (24.6%), HER2 – 117 (29.7%), and TNBC – 131 (33.2%). During follow up, 28 (7.1%) of the 394 patients had experienced tumor recurrence. In univariate Cox regression analysis, each of HER2-receptor status, pre-NAC tumor size, and pre-NAC axillary lymph node status were associated with recurrence. The hazard ratios, and their 95% confidence intervals (CI) and P values for these significant factors were as follows. HER2-receptor negative vs. positive: 2.5 (CI = 1.0-5.8; P = 0.036); cT1/2 vs. cT3/4: 2.2 (CI = 1.3-6.1; P = 0.008); cN0 vs. cN1-3: 9.5 (2.2-40.7; P = 0.002). However, age (&lt;50 vs. ≥50 y), residual DCIS, post-NAC axillary lymph node status, type of mastectomy (total vs. partial), and adjuvant radiation therapy were not associated with recurrence. Of the 28 patients with recurrence, site of first event was local for 8, and brain and visceral for 10 each. Seven of the 10 patients with brain metastasis were HER2-receptor positive. Eleven of the 28 patients with recurrence had deceased, with a median post-recurrence survival duration of 40 months (range = 2–94 months). Shorter survival was associated with HER2-receptor positivity (P = 0.003).
CONCLUSION
Axillary lymph node metastasis before rather than after NAC, and HER2-receptor positivity are associated with tumor recurrence in patients who achieved pCR in breast cancer. HER2-receptor positive patients had higher risk for brain metastasis and shorter survival. Given the extreme rarity of local recurrence after pCR, we cannot help but speculate that omitting surgical removal of pCR tissue may be permissible when pCR has been diagnosed accurately.
Citation Format: Asaoka M, Narui K, Suganuma N, Chishima T, Yamada A, Kawai S, Uenaka N, Sato E, Katsuta E, Kawaguchi T, Takabe K, Ishikawa T. Axillary lymph node metastasis and HER2-receptor positivity significantly associate with recurrence and worse survival in breast cancer patients who achieved pathological complete response after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-12.