Failure patterns according to molecular subtype in patients with invasive breast cancer following postoperative adjuvant radiotherapy: long-term outcomes in contemporary clinical practice.
OBJECTIVE
Although gene expression profiling provides critical information, knowledge remains limited regarding the differential effects of molecular subtype on clinical course. This study evaluated the impact of molecular status on long-term patterns of failure in patients with non-metastatic breast cancer.


METHODS
We analyzed data from 1181 individuals with invasive breast cancer undergoing surgery plus PORT from 2003 to 2011. Molecular subtypes were defined as luminal A (LA), luminal B (LB)-HER2(-), LB-HER2(+), HER2, and triple-negative (TN) based on the 2013 St. Gallen Consensus criteria. Competing risks analysis and baseline hazard rate function plots were used to explore subtype-specific recurrence patterns.


RESULTS
The 10-year overall survival rates of LA, LB-HER2(-), LB-HER2(+), HER2, and TN groups were 96, 93, 94, 84, and 85%, respectively (P < 0.001). Distant metastatic events differed significantly according to molecular subtype (P < 0.001). In competing risks regression analysis, initial development of distant metastasis was the highest with TN tumors, followed by HER2, LB-HER2(-), and LB-HER2(+) subtypes (P = 0.005). Regarding preferential sites of distant metastasis, the risk of initial brain metastasis was significantly higher with HER2 tumors, followed by TN tumors (P = 0.001). A low-level but sustained metastatic risk increment was observed in luminal tumors, whereas TN and HER2 subtypes showed a short-term risk surge within 5 years.


CONCLUSIONS
From the significant impact of molecular profile on distant metastasis, subtype-specific individualization of systemic treatment and close surveillance are suggested. The preferential and long-term risk of brain metastasis in the HER2 subtype underlines the importance of alternative anti-HER2 therapies.
Department of Radiation Oncology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-Do, 13620, Republic of Korea.
Yu Jin
YJ
Lim
Department of Radiation Oncology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-Do, 13620, Republic of Korea.
Sea-Won
SW
Lee
Department of Radiation Oncology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-Do, 13620, Republic of Korea.
Noorie
N
Choi
Department of Radiation Oncology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-Do, 13620, Republic of Korea.
Jeanny
J
Kwon
Department of Radiation Oncology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-Do, 13620, Republic of Korea.|Breast Care Center, Seoul National University Bundang Hospital, Seoul National College of Medicine, Seongnam, Korea.
Keun-Yong
KY
Eom
Breast Care Center, Seoul National University Bundang Hospital, Seoul National College of Medicine, Seongnam, Korea.
Eunyoung
E
Kang
Breast Care Center, Seoul National University Bundang Hospital, Seoul National College of Medicine, Seongnam, Korea.
Eun-Kyu
EK
Kim
Department of Surgery, Daerim St. Mary's Hospital, Seoul, Korea.
Sung-Won
SW
Kim
Breast Care Center, Seoul National University Bundang Hospital, Seoul National College of Medicine, Seongnam, Korea.
Jee Hyun
JH
Kim
Breast Care Center, Seoul National University Bundang Hospital, Seoul National College of Medicine, Seongnam, Korea.
Yu Jung
YJ
Kim
Breast Care Center, Seoul National University Bundang Hospital, Seoul National College of Medicine, Seongnam, Korea.
Se Hyun
SH
Kim
Breast Care Center, Seoul National University Bundang Hospital, Seoul National College of Medicine, Seongnam, Korea.
So Yeon
SY
Park
Department of Radiation Oncology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-Do, 13620, Republic of Korea.
Jae-Sung
JS
Kim
Department of Radiation Oncology, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-Do, 13620, Republic of Korea. inah228@snu.ac.kr.|Breast Care Center, Seoul National University Bundang Hospital, Seoul National College of Medicine, Seongnam, Korea. inah228@snu.ac.kr.
In Ah
IA
Kim
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy* / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*
D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
Adjuvant radiotherapy; Breast neoplasms; Neoplasm metastasis; Recurrence; Subtype