A population-based recurrence risk management study of patients with pT1 node-negative HER2+\u2009breast cancer: a National Clinical Database study

Makoto Kubo,Kenji Tamura,Yasuyuki Kojima,Hiroaki Miyata,Takayuki Kadoya,Yutaka Yamamoto,Hiraku Kumamaru,Minoru Miyashita,Hiromitsu Jinno,Masaaki Kawai,Masayuki Nagahashi,Kenjiro Aogi,Naoki Hayashi,Kotaro Iijima,Masayuki Yoshida,Sota Asaga,Shigeru Imoto,Etsuyo Ogo,Naoki Niikura

doi:10.1007/s10549-019-05413-7

Abstract

PurposeRecurrence risk management of patients with small (≤ 2 cm), node-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains challenging. We studied the effects of adjuvant chemotherapy and/or trastuzumab and survival outcomes among these patients, using data from the population-based Japanese National Clinical Database (NCD).MethodsWe identified a cohort of 2736 breast cancer patients with HER2+ pT1N0 disease: 489 pT1a, 642 pT1b, and 1623 pT1c. The median observation period was 76 months, and the 5-year follow-up rate was 48.2%. The number of events was 212 for disease-free survival (DFS), 40 for breast cancer-specific survival, and 84 for overall survival (OS).ResultsThere were 24.5% of pT1a, 51.9% of pT1b, and 63.3% of pT1c patients who were treated systemically after surgery. OS in pT1b (logrank test; p = 0.03) and DFS in pT1c (logrank test; p < 0.001) were significantly improved in treated compared with untreated patients. In the Cox proportional hazards model, treated patients had significantly longer OS than untreated patients in pT1b (hazard ratio (HR) 0.20) and pT1c (HR 0.54) groups. Estrogen receptor-negative tumors was also a significant predictor of survival in pT1c (HR 2.01) but not pT1ab patients. Furthermore, HR was greater in patients aged ≤ 35 years (3.18) compared to that in patients aged 50–69 years in the pT1b group.ConclusionsNCD data revealed that systemic treatment improved OS in pT1bc but not in pT1a node-negative HER2+ breast cancer patients. Future observational research using big-sized data is expected to play an important role in optimizing treatment for patients with early-stage breast cancer.

Highlights

The incidence of stage I breast cancer has increased gradually to nearly half of all primary breast cancer cases because of detection of nonpalpable breast cancer using screening mammography in Japan as well as in Europe and the United States [1,2,3,4,5]
We identified a cohort of 2736 patients with Human epidermal growth factor receptor 2 (HER2)+ pT1N0M0 disease (Fig. 1)
In our study using retrospectively collected data from the Japanese Breast Cancer Registry (BCR) held within the National Clinical Database (NCD), we identified 2736 patients with early-stage pT1N0 HER2+ breast cancer and demonstrated significantly improved survival benefits (DFS: Hazard ratio (HR) 0.45; 95% Confidence interval (CI) 0.32–0.68 and overall survival (OS): HR 0.54; 95% CI 0.31–0.94) in those who received systemic treatment in the pT1c group (Table 2)

Summary

Introduction

The incidence of stage I breast cancer has increased gradually to nearly half of all primary breast cancer cases because of detection of nonpalpable breast cancer using screening mammography in Japan as well as in Europe and the United States [1,2,3,4,5]. According to breast cancer registry, there was a marked increase from 37.3 to 51.6% in the proportion of stage I breast cancer patients during the year 2004 to 2014 [1]. HER2-overexpressing or HER2-amplified breast cancer accounts for 20–30% of invasive breast carcinomas [8], and without treatment, has the worst prognosis among subtypes [7]. Various guidelines support the use of trastuzumab-based chemotherapy as a standard option in tumors larger than 1 cm, and suggest its administration in T1b tumors because some studies have reported that HER2 overexpression was an independent, poor prognostic factor even for patients with pT1ab node-negative HER2+ breast cancer [6, 9]

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