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์ „์‹ ์น˜๋ฃŒ ํ›„ ์žฅ๊ธฐ๊ฐ„ ์ข…์–‘์˜ ์œ ์ง€๋ฅผ ๋ณด์ด๋Š” ์ „์ด์„ฑ ์œ ๋ฐฉ์•” ํ™˜์ž์˜ ์ž„์ƒ์  ํŠน์ง•

Abstract

Purpose

This study aimed to analyze the basic clinical characteristics and survival of patients with breast cancer whose disease had been stably maintained for more than 24 months after systemic therapy.

Methods

We retrospectively reviewed the medical records of patients with primary breast cancer who underwent surgery. Among these patients, patients with stage IV disease at diagnosis or those who developed distant metastasis during the follow-up period after surgery were included in this analysis. Patients whose disease remained stable for more than 24 months were classified as the long-term stable disease group. The remaining patients were classified as the control group.

Results

A total of 245 patients were eligible for this analysis. Patients in the long-term stable disease group showed a lower rate of histologic type III, a higher rate of hormone receptor positivity, and received less adjuvant chemotherapy. In the long-term stable disease group, the most frequent site of metastasis was the lungs, whereas in the control group, it was the bones. Overall survival was significantly better in the long-term stable disease group than in the control group (p<0.001). In univariate analysis, factors affecting the overall survival rate were the duration from diagnosis to metastasis, the absence of lymphatic infiltration, and the presence of hormone receptors. In multivariate analysis, the duration from diagnosis to metastasis and the absence of lymphatic infiltration were significant factors affecting the overall survival rate.

Conclusion

Disease progression was observed in many patients even after the disease had been stable for more than 24 months after systemic therapy. Although these patients had better outcomes compared with the others, continuous observation and possible additional treatment might be helpful for some patients.

์„œ ๋ก 

์ „์ด์„ฑ ์œ ๋ฐฉ์•” ํ™˜์ž์˜ ํ‰๊ท  ์ˆ˜๋ช…์€ ์•ฝ 2โ€“4๋…„ ์ •๋„๋กœ ์•Œ๋ ค์ ธ ์žˆ๋‹ค[1]. ๊ทธ๋Ÿฌ๋‚˜ ์ตœ๊ทผ ์—ฌ๋Ÿฌ ์น˜๋ฃŒ๋ฒ•์˜ ๋ฐœ๋‹ฌ์— ํž˜์ž…์–ด, ์›๊ฒฉ ์ „์ด๋œ ๊ฒฝ์šฐ๋„ ์ƒ์กด์œจ์ด ๋งŽ์ด ํ–ฅ์ƒ๋˜์—ˆ๋‹ค. ๋“œ๋ฌผ๊ฒŒ๋Š” ์ง„๋‹จ ํ›„ 18๋…„ ์ด์ƒ๊นŒ์ง€ ์žฅ๊ธฐ ์ƒ์กดํ•˜๋Š” ๊ฒฝ์šฐ๋„ ๋ณด๊ณ  ๋˜์—ˆ๋‹ค[2]. ํ•˜์ง€๋งŒ ์ด๋ ‡๊ฒŒ ์žฅ๊ธฐ ์ƒ์กดํ•˜๋Š” ํ™˜์ž๋“ค์˜ ์น˜๋ฃŒ์™€ ์ถ”์ ๊ด€์ฐฐ์— ๋Œ€ํ•œ ์ž„์ƒ์  ์ง€์นจ์€ ๊ฑฐ์˜ ์—†๋‹ค. ํŠนํžˆ ํŠน์ • ์•ฝ๋ฌผ์„ ์‚ฌ์šฉํ•˜์—ฌ ์žฅ๊ธฐ๊ฐ„ ์•ˆ์ • ๋ณ‘๋ณ€(stable disease)์ด ์œ ์ง€๋˜๋Š” ๊ฒฝ์šฐ ์ด ์•ฝ๋ฌผ์„ ์–ธ์ œ๊นŒ์ง€ ์‚ฌ์šฉํ•˜์—ฌ์•ผ ํ• ์ง€์— ๋Œ€ํ•œ ๊ฒฐ์ •์€ ์˜์‚ฌ์™€ ํ™˜์ž ๋ชจ๋‘์—๊ฒŒ ๋งค์šฐ ์–ด๋ ค์šด ์ผ์ด๋‹ค.
์ „์ด ์œ ๋ฐฉ์•”์˜ ์น˜๋ฃŒ๋Š” ์ข…์–‘์˜ ๋ถ„์ž์ƒ๋ฌผํ•™์  ํŠน์„ฑ๊ณผ ํ™˜์ž์˜ ์ „์‹  ๊ฑด๊ฐ• ์ƒํƒœ๋ฅผ ๊ณ ๋ คํ•˜์—ฌ ํ˜ธ๋ฅด๋ชฌ์š”๋ฒ•, ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•, ํ‘œ์ ์น˜๋ฃŒ ์ค‘ ์ ์ ˆํ•œ ์•ฝ์ œ๋ฅผ ์„ ํƒํ•˜์—ฌ ์‹œํ–‰ํ•œ๋‹ค.
ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์„ ์žฅ๊ธฐ๊ฐ„ ํˆฌ์—ฌ ์‹œ ๋ฌด์ง„ํ–‰ ์ƒ์กด๊ธฐ๊ฐ„์ด ์—ฐ์žฅ๋˜์ง€๋งŒ ์ „์ฒด ์ƒ์กด๊ธฐ๊ฐ„์˜ ์ด์ต์€ ์—†๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์žˆ๋‹ค[3]. ์žฅ๊ธฐ๊ฐ„ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์„ ํˆฌ์—ฌํ•˜๋Š” ๊ฒƒ์ด ์ •ํ•ด์ง„ ํšŸ์ˆ˜์˜ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์„ ํˆฌ์—ฌํ•˜๊ณ  ์ค‘๋‹จํ•˜๋Š” ๊ฒƒ๋ณด๋‹ค ์•” ์ง„ํ–‰๊ณผ ์‚ฌ๋ง์„ ๊ฐ์†Œ์‹œํ‚ค๋Š” ํšจ๊ณผ๊ฐ€ ์žˆ์œผ๋‚˜, ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์˜ ๋…์„ฑ๊ณผ ํ™˜์ž์˜ ์‚ถ์˜ ์งˆ์„ ๊ณ ๋ คํ•˜์—ฌ ๋ณด๋ฉด ๋ชจ๋“  ํ™˜์ž์—๊ฒŒ ์ด๋ฅผ ์ผ๊ด„์ ์œผ๋กœ ์ ์šฉํ•˜๊ธฐ๋Š” ์–ด๋ ต๋‹ค[4].
ํ˜ธ๋ฅด๋ชฌ์š”๋ฒ•๊ณผ ํ‘œ์ ์น˜๋ฃŒ์˜ ๋ฐœ๋‹ฌ๋กœ ์ธํ•ด ํ˜ธ๋ฅด๋ชฌ์ˆ˜์šฉ์ฒด ์–‘์„ฑ ๋˜๋Š” human epidermal growth factor receptor 2 (HER2) ์–‘์„ฑ ์œ ๋ฐฉ์•”์˜ ๊ฒฝ์šฐ ์งˆ๋ณ‘์˜ ์ง„ํ–‰์„ ํšจ๊ณผ์ ์œผ๋กœ ์–ต์ œํ•˜๋ฉฐ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์— ๋น„ํ•˜์—ฌ ๋…์„ฑ์ด ๋‚ฎ์€ ์•ฝ์ œ๋ฅผ ์žฅ๊ธฐ๊ฐ„์œผ๋กœ ์‚ฌ์šฉํ•˜๊ธฐ ์ข€ ๋” ์šฉ์ดํ•˜๊ฒŒ ๋˜์—ˆ๋‹ค[5]. ๊ทธ๋Ÿฌ๋‚˜ ํƒ€๋ชฉ์‹œํŽœ์€ ํ๊ฒฝ ์ฆ์ƒ, ์•ˆ ๋…์„ฑ, ํ˜ˆ์ „์ฆ, ์ž๊ถ๋‚ด๋ง‰์•”์˜ ๋ถ€์ž‘์šฉ์ด ๋‚˜ํƒ€๋‚  ์ˆ˜ ์žˆ๋‹ค[6]. ์•„๋กœ๋งˆํƒ€์ œ ์–ต์ œ์ œ๋Š” ๊ณจ๋‹ค๊ณต์ฆ๊ณผ ๊ณจ์ ˆ์˜ ์œ„ํ—˜๋„๊ฐ€ ์ฆ๊ฐ€ํ•˜๋ฉฐ ๊ด€์ ˆํ†ต ๋“ฑ์˜ ๊ทผ๊ณจ๊ฒฉ๊ณ„ ๋ฐ ๊ด€์ ˆ์ฆ์ƒ ๋“ฑ์ด ํ™˜์ž์˜ ์ˆœ์‘๋„๋ฅผ ๋–จ์–ด๋œจ๋ฆฐ๋‹ค[7]. ํ˜„์žฌ ์ž„์ƒ์—์„œ HER2 ์–‘์„ฑ ์œ ๋ฐฉ์•” ํ™˜์ž์—๊ฒŒ ์‚ฌ์šฉ๋˜๋Š” ๋Œ€ํ‘œ์ ์ธ ํ‘œ์ ์น˜๋ฃŒ์ œ์ธ trastuzumab์€ HER2 ์–‘์„ฑ ์œ ๋ฐฉ์•”์—์„œ ์ „์ฒด ์ƒ์กด์œจ์˜ ํš๊ธฐ์ ์ธ ์ง„์ „์„ ๊ฐ€์ ธ์™”์ง€๋งŒ ๋ถ€์ž‘์šฉ์œผ๋กœ ์‹ฌ๋…์„ฑ์„ ์ผ์œผํ‚ฌ ์ˆ˜ ์žˆ์–ด ํˆฌ์—ฌ ์‹œ ์ฃผ์˜๋ฅผ ์š”ํ•œ๋‹ค[8]. ๋˜ ๋‹ค๋ฅธ ํ‘œ์  ์น˜๋ฃŒ์ œ๋กœ mechanistic target of rapamycin (mTOR) ์–ต์ œ์ œ์˜ ํ•˜๋‚˜์ธ everolimus๋Š” ์•„๋กœ๋งˆํƒ€์ œ ์–ต์ œ์ œ์™€์˜ ๋ณ‘์šฉ์š”๋ฒ•์—์„œ ์ž„์ƒ์  ์œ ์šฉ์„ฑ์„ ๋ณด์—ฌ์ฃผ์—ˆ์œผ๋‚˜ ๊ตฌ๊ฐ• ๊ถค์–‘, ๊ณ ํ˜ˆ๋‹น ๋“ฑ์œผ๋กœ ์ง€์† ์น˜๋ฃŒ๊ฐ€ ์‰ฝ์ง€ ์•Š๋‹ค[9,10]. ์ด์— ๋”ํ•˜์—ฌ ์•ฝ๋ฌผ์˜ ์น˜๋ฃŒ ํšจ๊ณผ๋ฅผ ํŒ๋‹จํ•˜๊ธฐ ์œ„ํ•˜์—ฌ 2โ€“4๊ฐœ์›” ๋งˆ๋‹ค ์ „์‚ฐํ™” ๋‹จ์ธต ์ดฌ์˜(computed tomography, CT) ๋“ฑ ๊ณ ๊ฐ€์˜ ์˜์ƒํ•™์  ๊ฒ€์‚ฌ๊ฐ€ ํ•„์š”ํ•˜๋‹ค[10]. ๋”ฐ๋ผ์„œ ์ „์ด์„ฑ ์œ ๋ฐฉ์•” ํ™˜์ž์—์„œ๋Š” ์œ„์™€ ๊ฐ™์€ ๋ถ€์ž‘์šฉ์œผ๋กœ ์ธํ•˜์—ฌ ์ƒ๊ธฐ๋Š” ํ™˜์ž์˜ ์‚ถ์˜ ์งˆ ์ €ํ•˜์™€ ์˜๋ฃŒ๋น„, ํ™˜์ž์˜ ์ƒ์กด๊ธฐ๊ฐ„ ์—ฐ์žฅ ๋“ฑ์„ ๋ณตํ•ฉ์ ์œผ๋กœ ๊ณ ๋ คํ•˜์—ฌ ์น˜๋ฃŒ ๋ฐฉ๋ฒ•๊ณผ ๊ธฐ๊ฐ„์„ ๊ฒฐ์ •ํ•ด์•ผ ํ•œ๋‹ค.
๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ์žฅ๊ธฐ๊ฐ„ ์ข…์–‘์˜ ์œ ์ง€(stable disease)๋ฅผ ๋ณด์ด๋Š” ์ „์ด์„ฑ ์œ ๋ฐฉ์•” ํ™˜์ž๋“ค์˜ ์ž„์ƒ์ ์ธ ํŠน์„ฑ๊ณผ ๋ฌด์ง„ํ–‰ ์ƒ์กด์œจ(progression-free survival), ์ „์ฒด ์ƒ์กด์œจ(overall survival)์— ๋ฏธ์น˜๋Š” ์š”์ธ๋“ค์„ ๋ถ„์„ํ•˜์˜€๋‹ค.

๋Œ€์ƒ ๋ฐ ๋ฐฉ๋ฒ•

๋Œ€์ƒ ํ™˜์ž

2004๋…„ 1์›”๋ถ€ํ„ฐ 2012๋…„ 12์›”๊นŒ์ง€ ํ•œ๊ตญ์›์ž๋ ฅ์˜ํ•™์›์—์„œ ์›๋ฐœ์„ฑ ์œ ๋ฐฉ์•”์œผ๋กœ ๊ทผ์น˜์  ์ˆ˜์ˆ ์„ ๋ฐ›์€ ํ›„ ์ถ”์ ๊ด€์ฐฐ ์ค‘์— ์›๊ฒฉ ์ „์ด๊ฐ€ ์ง„๋‹จ๋˜์—ˆ๊ฑฐ๋‚˜ ์œ ๋ฐฉ์•” ์ง„๋‹จ ์‹œ๋ถ€ํ„ฐ ์›๊ฒฉ ์ „์ด๊ฐ€ ๋™๋ฐ˜๋œ ํ™˜์ž๋ฅผ ๋Œ€์ƒ์œผ๋กœ ํ•˜์˜€๋‹ค. ์ด ์ค‘ ๋ฐ˜๋Œ€ํŽธ ์œ ๋ฐฉ์— ์ด์ฐจ์„ฑ ์œ ๋ฐฉ์•”์ด ๋ฐœ์ƒํ•œ ํ™˜์ž, ์œ ๋ฐฉ์•” ์™ธ์— ์›๋ฐœ์•”์œผ๋กœ ์ง„๋‹จ๋œ ํ™˜์ž, ์œ ๋ฐฉ์•” ์ด์™ธ์˜ ๋‹ค๋ฅธ ์ด์œ ๋กœ ์‚ฌ๋งํ•œ ํ™˜์ž, ์ „์ด ์ดํ›„ 2๊ฐœ์›” ์ด์ƒ์˜ ์ถ”์ ๊ด€์ฐฐ์ด ๋ถˆ๊ฐ€๋Šฅํ–ˆ๋˜ ํ™˜์ž, ์—ฝ์ƒ ์ข…์–‘ ํ™˜์ž, ์žฌ๋ฐœ ํ›„ ์ „์‹ ์  ์น˜๋ฃŒ(systemic therapy)๋ฅผ ์‹œํ–‰ํ•˜์ง€ ์•Š์€ ํ™˜์ž 427๋ช…์„ ์ œ์™ธํ•˜๊ณ , ์ตœ์ข… 245๋ช…์ด ๋ณธ ์—ฐ๊ตฌ์— ํฌํ•จ๋˜์—ˆ๋‹ค.
๊ทผ์น˜์  ์ˆ˜์ˆ  ์‹œํ–‰ ํ›„ ์ถ”์ ๊ด€์ฐฐ์„ ์‹œํ–‰ํ•˜์˜€์œผ๋ฉฐ, ์ง„๋‹จ ๋‹น์‹œ ์ „์ด๊ฐ€ ํ™•์ธ๋œ ๊ฒฝ์šฐ ์ถœํ˜ˆ, ๊ดด์‚ฌ๊ฐ€ ์žˆ๊ฑฐ๋‚˜ ์ด์™€ ๊ฐ™์€ ์ฆ์ƒ์ด ๋‚˜ํƒ€๋‚  ๊ฒƒ์ด ์˜ˆ์ƒ๋˜๋Š” ํ™˜์ž๋ฅผ ๋Œ€์ƒ์œผ๋กœ ๋ณ‘๋ณ€๊ณผ ์ฆ์ƒ์˜ ์กฐ์ ˆ์„ ์œ„ํ•ด ๊ณ ์‹์  ์ˆ˜์ˆ ์ด ์‹œํ–‰๋˜์—ˆ๋‹ค. ์ˆ˜์ˆ  ํ›„ 5๋…„๊นŒ์ง€๋Š” 6๊ฐœ์›” ๊ฐ„๊ฒฉ์œผ๋กœ ํ˜ˆ์•ก ์ข…์–‘ํ‘œ์ง€์ž๊ฒ€์‚ฌ, ์œ ๋ฐฉ์ดฌ์˜์ˆ , ์œ ๋ฐฉ์ดˆ์ŒํŒŒ, ๋ณต๋ถ€ ๋ฐ ํ‰๋ถ€ CT, ๊ณจ์Šค์บ”์„ ์‹œํ–‰ํ•˜์˜€๋‹ค. 5๋…„ ์ดํ›„์—๋Š” 1๋…„ ๊ฐ„๊ฒฉ์œผ๋กœ ์ถ”์ ๊ด€์ฐฐ์„ ์‹œํ–‰ํ•˜์˜€๋‹ค. ์›๊ฒฉ ์ „์ด๊ฐ€ ๋ฐœ๊ฒฌ๋œ ์ดํ›„์—๋Š” 2โ€“3๊ฐœ์›” ๊ฐ„๊ฒฉ์œผ๋กœ ํ˜ˆ์•ก ์ข…์–‘ํ‘œ์ง€์ž ๊ฒ€์‚ฌ, ์œ ๋ฐฉ์ดฌ์˜์ˆ , ์œ ๋ฐฉ์ดˆ์ŒํŒŒ, ํ‰๋ถ€ ๋ฐ ๋ณต๋ถ€ CT, ๊ณจ์Šค์บ” ์ค‘ ํ™˜์ž์˜ ์ „์ด ๋ถ€์œ„์™€ ์น˜๋ฃŒ ์ผ์ •์— ๋”ฐ๋ผ ์„ ํƒํ•˜์—ฌ ์ถ”์ ๊ด€์ฐฐ์„ ์‹œํ–‰ํ•˜์˜€๋‹ค.
์ˆ˜์ˆ  ํ›„์— ํ•ญ์•”ํ™”ํ•™์š”๋ฒ• ์‹œํ–‰ ์ค‘์— ์ „์ด๊ฐ€ ๋ฐœ์ƒํ•˜์˜€๋˜ ํ™˜์ž๋“ค์€ ๋ณด์กฐ ํ˜ธ๋ฅด๋ชฌ์š”๋ฒ•์„ ๋ฐ›์ง€ ๋ชปํ•˜์˜€๋‹ค. ์ง„๋‹จ ์‹œ์— ์ „์ด๊ฐ€ ๋ฐœ์ƒ๋˜์—ˆ๋˜ ํ™˜์ž ์—ญ์‹œ ๋ณด์กฐ ํ˜ธ๋ฅด๋ชฌ์š”๋ฒ•์„ ์‹œํ–‰ ๋ฐ›์ง€ ๋ชปํ•˜์˜€๋‹ค. ๋”ฐ๋ผ์„œ 67๋ช…์˜ ํ™˜์ž๋งŒ์ด ๊ทผ์น˜์  ์ˆ˜์ˆ  ํ›„ ๋ณด์กฐ ํ˜ธ๋ฅด๋ชฌ์š”๋ฒ•์„ ์‹œํ–‰ ๋ฐ›์•˜๋‹ค.
์ „์‹ ์ „์ด๊ฐ€ ์ง„๋‹จ๋˜๊ณ  ์ „์‹ ์  ์น˜๋ฃŒ๋ฅผ ๋ฐ›์€ ํ›„ ํ•œ ๋ฒˆ์ด๋ผ๋„ 24๊ฐœ์›”์„ ์ดˆ๊ณผํ•˜์—ฌ ์•ˆ์ • ๋ณ‘๋ณ€์œผ๋กœ ์œ ์ง€๋œ ํ™˜์ž๋ฅผ ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ(long-term stable disease group)์œผ๋กœ ์ •์˜ํ•˜์˜€์œผ๋ฉฐ ๊ทธ ์™ธ์˜ ๋ชจ๋“  ํ™˜์ž๋ฅผ ๋Œ€์กฐ๊ตฐ์œผ๋กœ ์ •์˜ํ•˜์˜€๋‹ค.

์ž๋ฃŒ ์ˆ˜์ง‘

์œ ๋ฐฉ์•”์œผ๋กœ ์ง„๋‹จ๋ฐ›๊ณ  ์ˆ˜์ˆ ์„ ์‹œํ–‰ ๋ฐ›์€ ํ™˜์ž๋“ค์˜ ์˜๋ฌด๊ธฐ๋ก๊ณผ ๋ณ‘๋ฆฌ ์ž๋ฃŒ๋ฅผ ๋ฐ”ํƒ•์œผ๋กœ ์กฐ์‚ฌํ•˜์˜€๋‹ค. ์ˆ˜์ˆ  ๋ฐฉ๋ฒ•, ์ˆ˜์ˆ  ๋‹น์‹œ์˜ ๋‚˜์ด, TNM ๋ณ‘๊ธฐ, ์กฐ์งํ•™์  ๋“ฑ๊ธ‰, ํ˜ธ๋ฅด๋ชฌ์ˆ˜์šฉ์ฒด, HER2 ๋ฐœํ˜„ ์œ ๋ฌด, Ki-67 ๋ฐœํ˜„ ์œ ๋ฌด, ์ˆ˜์ˆ  ํ›„ ์‹œํ–‰ํ•œ ๋ณด์กฐ ์น˜๋ฃŒ, ์ „์ด์žฅ๊ธฐ ๋“ฑ ์›๋ฐœ ์ข…์–‘์˜ ์ž„์ƒ๋ณ‘๋ฆฌํ•™์ ์ธ ํŠน์ง•์„ ํ›„ํ–ฅ์ ์œผ๋กœ ๋ถ„์„ํ•˜์˜€๋‹ค. ์—์ŠคํŠธ๋กœ๊ฒ ์ˆ˜์šฉ์ฒด ํ˜น์€ ํ”„๋กœ๊ฒŒ์Šคํ…Œ๋ก  ์ˆ˜์šฉ์ฒด ์–‘์„ฑ์ธ ๊ฒฝ์šฐ๋ฅผ ํ˜ธ๋ฅด๋ชฌ์ˆ˜์šฉ์ฒด ์–‘์„ฑ์œผ๋กœ ์ •์˜ํ•˜์˜€๋‹ค. HER2 ์–‘์„ฑ์€ ๋ฉด์—ญ์กฐ์งํ™”ํ•™์—ผ์ƒ‰์—์„œ 3+์ธ ๊ฒฝ์šฐ๋กœ ์ •์˜ํ•˜์˜€๋‹ค. HER2๊ฐ€ ๋ฉด์—ญ์กฐ์งํ™”ํ•™์—ผ์ƒ‰์—์„œ 2+์ธ ๊ฒฝ์šฐ fluorescence in situ hybridization (FISH) ๋˜๋Š” silver-enhanced in situ hybridization (SISH)์—์„œ HER2/CEP17 ๋น„์œจ์ด >2.2์ธ ๊ฒฝ์šฐ๋ฅผ ์–‘์„ฑ์œผ๋กœ ์ •์˜ํ•˜์˜€๋‹ค.
๋ณธ ์—ฐ๊ตฌ๋Š” ํ•œ๊ตญ์›์ž๋ ฅ์˜ํ•™์› ์ž„์ƒ์—ฐ๊ตฌ ์œค๋ฆฌ์‹ฌ์˜์œ„์›ํšŒ์˜ ์Šน์ธ์„ ๋ฐ›์•˜๋‹ค(K-1605-002-015).

ํ†ต๊ณ„ ๋ฐฉ๋ฒ•

์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ๊ณผ ๊ทธ ์™ธ์˜ ๋Œ€์กฐ๊ตฐ ์‚ฌ์ด์— ์ž„์ƒ๋ณ‘๋ฆฌํ•™์ ์ธ ์ฐจ์ด๋Š” Pearson chi-square test์™€ Student t-test๋ฅผ ์ด์šฉํ•˜์—ฌ ๋ถ„์„ํ•˜์˜€๋‹ค. ๋ฌด์ง„ํ–‰ ์ƒ์กด์œจ๊ณผ ์ „์ฒด ์ƒ์กด์œจ์€ Kaplan-Meier ๋ฐฉ๋ฒ•์„ ์ด์šฉํ•˜์—ฌ ๋ถ„์„ํ•˜์˜€๋‹ค. ์ „์ฒด ์ƒ์กด์œจ์— ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ์š”์†Œ๋Š” log-rank test๋กœ ๋น„๊ตํ•˜์˜€์œผ๋ฉฐ ์ด ๋ถ„์„์—์„œ ์˜๋ฏธ ์žˆ๋Š” ๋ณ€์ˆ˜๋ฅผ ์ด์šฉํ•˜์—ฌ Cox proportional hazard model์„ ํ†ตํ•ด ๋‹ค๋ณ€๋Ÿ‰ ๋ถ„์„์„ ์‹œํ–‰ํ•˜์˜€๋‹ค. ๋ชจ๋“  ํ†ต๊ณ„์  ๋ถ„์„์€ p-value <0.05๋ฅผ ํ†ต๊ณ„์ ์œผ๋กœ ์˜๋ฏธ ์žˆ๋Š” ๊ฐ’์œผ๋กœ ๋ณด์•˜๋‹ค.

๊ฒฐ ๊ณผ

์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์€ 55๋ช…์ด์—ˆ์œผ๋ฉฐ ๋Œ€์กฐ๊ตฐ์€ 190๋ช…์ด์—ˆ๋‹ค. ์œ ๋ฐฉ์•” ์ง„๋‹จ ๋‹น์‹œ์˜ ๋‚˜์ด(p=0.223), ์œ ๋ฐฉ์•” ์ง„๋‹จ ํ›„ ์‹œํ–‰ํ•œ ๊ทผ์น˜์  ์ ˆ์ œ ์ˆ˜์ˆ ์˜ ์ข…๋ฅ˜(p=0.192), ์›๋ฐœ ์ข…์–‘์˜ ํฌ๊ธฐ(p=0.320), ๋ฆผํ”„์ ˆ ์ „์ด ์—ฌ๋ถ€(p=0.160), ์ˆ˜์ˆ  ๋‹น์‹œ์˜ ํƒ€ ์žฅ๊ธฐ ์ „์ด ์—ฌ๋ถ€(p=0.060)๋Š” ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ๊ณผ ๋Œ€์กฐ๊ตฐ ์‚ฌ์ด์— ์ฐจ์ด๊ฐ€ ์—†์—ˆ๋‹ค. ๋˜ํ•œ ์œ ๋ฐฉ์•” ์ง„๋‹จ ๋‹น์‹œ ์›๊ฒฉ ์ „์ด์˜ ๋™๋ฐ˜์€ ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์—์„œ ๋งŽ์€ ๋น„์œจ์„ ๋ณด์˜€์œผ๋‚˜ ํ†ต๊ณ„์ ์ธ ์œ ์˜ํ•œ ์ฐจ์ด๋Š” ๋ณด์ด์ง€ ์•Š์•˜๋‹ค.
์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์˜ ์กฐ์งํ•™์  ๋ถ„ํ™”๋„ III์ธ ํ™˜์ž๋Š” 18๋ช…(32.7%), ๋Œ€์กฐ๊ตฐ์˜ ์กฐ์งํ•™์  ๋ถ„ํ™”๋„๊ฐ€ III ์ธ ํ™˜์ž๋Š” 89๋ช…(46.8%)์œผ๋กœ ๋Œ€์กฐ๊ตฐ์—์„œ ์กฐ์งํ•™์  ๋ถ„ํ™”๋„๊ฐ€ III์ธ ํ™˜์ž๊ฐ€ ๋†’์€ ๋น„์œจ์„ ๋ณด์˜€๋‹ค(p=0.004). ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์—์„œ ํ˜ธ๋ฅด๋ชฌ์ˆ˜์šฉ์ฒด๊ฐ€ ์–‘์„ฑ์ธ ํ™˜์ž๋Š” 46๋ช…(83.6%), ๋Œ€์กฐ๊ตฐ์˜ ํ˜ธ๋ฅด๋ชฌ์ˆ˜์šฉ์ฒด๊ฐ€ ์–‘์„ฑ์ธ ํ™˜์ž๋Š” 117๋ช…(61.6%)์œผ๋กœ ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์—์„œ ํ˜ธ๋ฅด๋ชฌ์ˆ˜์šฉ์ฒด ์–‘์„ฑ์ธ ํ™˜์ž์˜ ๋น„์œจ์ด ๋” ๋†’์•˜๋‹ค(p=0.002). ๋ฐ˜๋ฉด HER2 ๊ณผ๋ฐœํ˜„ ์—ฌ๋ถ€(p=0.386)์™€ Ki-67 ์ˆ˜์น˜(p=0.560)๋Š” ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ๊ณผ ๋Œ€์กฐ๊ตฐ์—์„œ ์ฐจ์ด๋ฅผ ๋ณด์ด์ง€ ์•Š์•˜๋‹ค. ๊ทผ์น˜์  ์ˆ˜์ˆ  ์‹œํ–‰ 2๋…„ ์ดํ›„ ์ „์ด๊ฐ€ ์ง„๋‹จ๋œ ๊ฒฝ์šฐ๋Š” ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์—์„œ 54.5%๋กœ ๋Œ€์กฐ๊ตฐ 42.6%๊ณผ ํ†ต๊ณ„ํ•™์ ์ธ ์ฐจ์ด๊ฐ€ ์—†์—ˆ๋‹ค(p=0.080) (Table 1). ๋ณธ ๋…ผ๋ฌธ์—์„œ๋Š” ์ง„๋‹จ ์‹œ ์ „์ด๊ฐ€ ์žˆ๋˜ ํ™˜์ž์™€ ์น˜๋ฃŒ ์ค‘ ์ „์ด๊ฐ€ ์žˆ์—ˆ๋˜ ํ™˜์ž๋ฅผ ๊ฐ™์ด ๋ถ„์„ํ•˜์˜€๋‹ค. ๊ทธ ์ด์œ ๋Š” ๋ณธ ์—ฐ๊ตฌ์˜ ๋ชฉ์ ์ด ์›๊ฒฉ ์ „์ด๊ฐ€ ์žˆ๋Š” ํ™˜์ž์—๊ฒŒ์„œ ์•ฝ๋ฌผ์น˜๋ฃŒ๋ฅผ ํ•˜์˜€์„ ๋•Œ ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž์˜ ํŠน์„ฑ์„ ๋ณด๊ณ ์ž ํ•˜์˜€๊ธฐ ๋•Œ๋ฌธ์— ๋‘ ๊ตฐ์˜ ํ™˜์ž๋ฅผ ๋ชจ๋‘ ํฌํ•จ์‹œ์ผฐ๋‹ค. ํ†ต๊ณ„์  ๋ถ„์„์—์„œ๋„ Table 1์— ๋‚˜ํƒ€๋‚œ ๋ฐ”์™€ ๊ฐ™์ด ๋‘ ๊ตฐ ๊ฐ„์˜ ํ†ต๊ณ„ํ•™์ ์œผ๋กœ ์œ ์˜ํ•œ ์ฐจ์ด๋Š” ๊ด€์ฐฐ ํ•  ์ˆ˜ ์—†์—ˆ๋‹ค.
์ „์ด ์žฅ๊ธฐ๋ณ„ ๋ถ„๋ฅ˜๋กœ ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์—์„œ๋Š” ํ์ „์ด๊ฐ€ ๊ฐ€์žฅ ๋งŽ์€ 27๋ช…(49.1%), ๊ทธ ๋‹ค์Œ์œผ๋กœ ๋ผˆ์ „์ด 18๋ช…(32.7%)์ด ๋งŽ์•˜๋‹ค. ๋Œ€์กฐ๊ตฐ์—์„œ๋Š” ๋ผˆ์ „์ด๊ฐ€ ๊ฐ€์žฅ ๋งŽ์€ 99๋ช…(52.1%), ๊ทธ ๋‹ค์Œ์œผ๋กœ ํ์ „์ด 74๋ช…(38.9%), ๊ฐ„์ „์ด 46๋ช…(24.2%)์˜ ์ˆœ์ด์—ˆ๋‹ค(Table 2).
ํ‰๊ท  ๋ฌด์ง„ํ–‰ ์ƒ์กด์œจ์€ 67.3๊ฐœ์›”์ด์—ˆ๊ณ  ์ค‘์•™๊ฐ’์€ 69.0๊ฐœ์›”์ด์—ˆ๋‹ค(Figure 1). ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์—์„œ 24๊ฐœ์›” ์ด์ƒ ์žฅ๊ธฐ ์•ˆ์ • ์‹œ ์‚ฌ์šฉํ•œ ์ „์‹  ์•ฝ๋ฌผ์„ ์‹œ์ž‘ํ•œ ์‹œ์ ๋ถ€ํ„ฐ ๋ฌด์ง„ํ–‰ ์ƒ์กด ๊ณก์„ ์„ ํ™•์ธํ•˜์—ฌ ๋ณด์•˜๋‹ค. ํ™˜์ž๋“ค์€ 2๋…„๊ฐ„ ์žฅ๊ธฐ ์•ˆ์ • ํ›„์—๋„ ์ง€์†์ ์ธ ์งˆ๋ณ‘์˜ ์ง„ํ–‰์„ ๋ณด์˜€์œผ๋ฉฐ ์ด๋Ÿฌํ•œ ๊ฒฝํ–ฅ์€ ์ด ํ›„ 60๊ฐœ์›”๊นŒ์ง€๋„ ์ง€์†๋˜์—ˆ๋‹ค. ์›๊ฒฉ ์ „์ด ์ง„๋‹จ ํ›„ ์ „์ฒด ์ƒ์กด์œจ์—์„œ๋Š” ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์ด ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•˜์—ฌ ์ข‹์€ ์ „์ฒด ์ƒ์กด์œจ์„ ๋ณด์˜€๋‹ค(p<0.001) (Figure 2).
์ˆ˜์ˆ  ํ›„ ์ฒซ ๋ฒˆ์งธ ์ „์ด๊ฐ€ ์ง„๋‹จ ๋œ ์‹œ๊ธฐ๊ฐ€ 24๊ฐœ์›” ์ด์ƒ์ธ ๊ฒฝ์šฐ(p<0.001), ๋ณ‘๋ณ€์˜ ์žฅ๊ธฐ ์•ˆ์ • ์ƒํƒœ๊ฐ€ 24๊ฐœ์›” ์ด์ƒ ์œ ์ง€๋œ ๊ฒฝ์šฐ(p<0.001), ๋ฆผํ”„๊ด€ ์นจ์œค์ด ์—†๋Š” ๊ฒฝ์šฐ(p=0.041), ํ˜ธ๋ฅด๋ชฌ์ˆ˜์šฉ์ฒด ์–‘์„ฑ์ธ ๊ฒฝ์šฐ(p<0.001)๊ฐ€ ํ†ต๊ณ„ํ•™์ ์œผ๋กœ ์œ ์˜ํ•˜๊ฒŒ ์ „์ฒด ์ƒ์กด์œจ์ด ์ข‹์•˜๋‹ค(Table 3).
๋‹จ๋ณ€๋Ÿ‰ ๋ถ„์„์—์„œ ์˜๋ฏธ ์žˆ์—ˆ๋˜ ์ธ์ž๋กœ ๋‹ค๋ณ€๋Ÿ‰ ๋ถ„์„์„ ์‹œํ–‰ํ•˜์˜€๋‹ค. ์ˆ˜์ˆ  ํ›„ ์ฒซ ๋ฒˆ์งธ ์ „์ด๊ฐ€ ์ง„๋‹จ ๋œ ์‹œ๊ธฐ(hazard ratio, 6.862; 95% confidence interval [CI], 3.792โ€“12.418; p<0.001), ๋ณ‘๋ณ€์˜ ์žฅ๊ธฐ ์•ˆ์ • ์ƒํƒœ๊ฐ€ 24๊ฐœ์›” ์ด์ƒ ์œ ์ง€๋œ ๊ฒฝ์šฐ(hazard ratio, 11.586; 95% CI, 3.589โ€“37.399; p<0.001), ๋ฆผํ”„๊ด€ ์นจ์œค์ด ์—†๋Š” ๊ฒฝ์šฐ(hazard ratio, 1.866; 95% CI, 1.026โ€“3.401; p=0.041)๊ฐ€ ์ „์ฒด ์ƒ์กด์œจ์— ์ข‹์€ ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ๋…๋ฆฝ์ ์ธ ๋ณ€์ˆ˜๋กœ ํ™•์ธ๋˜์—ˆ๋‹ค(Table 4).

๊ณ  ์ฐฐ

๋ณธ ์—ฐ๊ตฌ์—์„œ 2๋…„ ์ด์ƒ ์žฅ๊ธฐ ์•ˆ์ • ๋ณ‘๋ณ€์œผ๋กœ ์œ ์ง€๋œ ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์€ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด์„œ ์ „์ฒด ์ƒ์กด์œจ์€ ์ข‹์•˜์œผ๋‚˜, ์žฅ๊ธฐ์ ์œผ๋กœ๋Š” ๋ณ‘์˜ ์ง„ํ–‰์ด ์ง€์†์ ์œผ๋กœ ๊ด€์ฐฐ๋˜์—ˆ๋‹ค. ์ด์™€ ๊ฐ™์ด ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž๊ตฐ์˜ ์ „์ฒด ์ƒ์กด์œจ์ด ๋†’์€ ์ด์œ ๋Š” ์œ ๋ฐฉ์•” ์žฌ๋ฐœ ํ›„ 24๊ฐœ์›” ์ด์ƒ ์ข…์–‘์˜ ์œ ์ง€๋ฅผ ๋ณด์ธ ํ™˜์ž๋“ค์€ ํ˜ธ๋ฅด๋ชฌ์ˆ˜์šฉ์ฒด ์–‘์„ฑ, HER2 ์Œ์„ฑ์„ ๋ณด์ด๋Š” ๊ฒฝ์šฐ๊ฐ€ ๋งŽ๊ธฐ ๋•Œ๋ฌธ์ด์—ˆ์„ ๊ฒƒ์ด๋‹ค. ์ด๋Ÿฌํ•œ ํ™˜์ž๋Š” ์ƒ์กด์œจ์ด ์ข‹์€ ๊ฒƒ์œผ๋กœ ์ด๋ฏธ ์•Œ๋ ค์ ธ ์žˆ๋‹ค[11-14]. ๋˜ํ•œ ํ˜ธ๋ฅด๋ชฌ์š”๋ฒ•์€ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์— ๋น„ํ•˜์—ฌ ๋…์„ฑ์ด ์ ์–ด ๋ช‡ ๋…„๊ฐ„์˜ ์žฅ๊ธฐ์  ์น˜๋ฃŒ๋„ ๊ฐ€๋Šฅํ•˜๊ธฐ ๋•Œ๋ฌธ์— ์ด๋Ÿฐ ํ™˜์ž์—์„œ ์ƒ์กด์œจ์ด ์ฆ๊ฐ€ํ•˜๋Š” ๋ฐ ๋„์›€์ด ๋˜์—ˆ์„ ๊ฒƒ์ด๋‹ค[5].
๋ณธ ์—ฐ๊ตฌ์—์„œ์˜ ํŠน์ดํ•œ ์ ์€ ์žฅ๊ธฐ ์•ˆ์ • ํ™˜์ž์—์„œ์˜ ์ „์ด ์žฅ๊ธฐ ์ค‘ ํ์ „์ด๊ฐ€ ๊ฐ€์žฅ ๋งŽ์•˜๋‹ค๋Š” ๊ฒƒ์ด๋‹ค. ์ผ๋ฐ˜์ ์œผ๋กœ ์œ ๋ฐฉ์•”์˜ ์ผ์ฐจ ์น˜๋ฃŒ ํ›„ ์žฌ๋ฐœ ํ™˜์ž์˜ ์ „์ด ์žฅ๊ธฐ๋Š” ๋ผˆ์ „์ด๊ฐ€ ๊ฐ€์žฅ ๋งŽ์œผ๋ฉฐ ํ์ „์ด๊ฐ€ ์žˆ์„ ๊ฒฝ์šฐ ๋ผˆ์ „์ด์— ๋น„ํ•˜์—ฌ ์˜ˆํ›„๊ฐ€ ์•ˆ ์ข‹๋‹ค๊ณ  ์•Œ๋ ค์ ธ ์žˆ๋‹ค[15-17]. ๊ทธ๋Ÿฌ๋‚˜ ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ์žฅ๊ธฐ ์œ ์ง€ ํ™˜์ž๊ตฐ์—์„œ ์ฐจ์ง€ํ•˜๋Š” ๋น„์œจ์ด ํ์ „์ด, ๋ผˆ์ „์ด, ๋ฆผํ”„์ ˆ์ „์ด์˜ ์ˆœ์œผ๋กœ ๋‚˜ํƒ€๋‚˜ ํ์ „์ด ํ™˜์ž๊ฐ€ ์ƒ๋Œ€์ ์œผ๋กœ ๋†’์€ ์ƒ์กด์œจ์„ ๋ณด์˜€๋‹ค. ์ด์™€ ๊ฐ™์€ ๊ฒฐ๊ณผ๋Š” ์ง€๊ธˆ๊นŒ์ง€ ์•Œ๋ ค์ง„ ๋‚ด์šฉ๊ณผ๋Š” ๋‹ค๋ฅธ ๊ฒƒ์œผ๋กœ ๊ทธ ์ด์œ ๋Š” ๋ช…ํ™•ํ•˜์ง€ ์•Š์œผ๋‚˜ ์ตœ๊ทผ ๊ธ‰์†ํžˆ ๋ฐœ๋‹ฌํ•œ ์œ ๋ฐฉ์•” ์ „์‹ ์น˜๋ฃŒ ์•ฝ๋ฌผ์— ํž˜ ์ž…์—ˆ์„ ๊ฐ€๋Šฅ์„ฑ์ด ์žˆ๋‹ค. Gerratana ๋“ฑ[18]์ด ์ตœ๊ทผ ๋ฐœํ‘œํ•œ ๋ฐ”์— ์˜ํ•˜๋ฉด ์ฒซ ๋ฒˆ์งธ ์œ ๋ฐฉ์•”์˜ ์›๊ฒฉ ์ „์ด๊ฐ€ ํ์ „์ด์ธ ๊ฒฝ์šฐ์—๋Š” ์ „์ด ํ›„ ์ƒ์กด๊ธฐ๊ฐ„์€ 58.5๊ฐœ์›”๋กœ ๊ฐ€์žฅ ์ข‹์€ ์˜ˆํ›„๋ฅผ ๋ณด์˜€๊ณ , ๋ผˆ์ „์ด์˜ ๊ฒฝ์šฐ 44.4๊ฐœ์›”๋กœ ๋‘ ๋ฒˆ์งธ์˜€๋‹ค. ๊ทธ ๋’ค๋กœ ๊ฐ„์ „์ด์ธ ๊ฒฝ์šฐ๊ฐ€ 36.7๊ฐœ์›”, ๋‡Œ์ „์ด์ธ ๊ฒฝ์šฐ๊ฐ€ 7.35๊ฐœ์›”๋กœ ๋ณด๊ณ ํ•˜์—ฌ ๋ณธ ์—ฐ๊ตฌ ๊ฒฐ๊ณผ์™€ ์ผ์น˜ํ•˜์˜€๋‹ค. ์ด๋Š” ํ˜ธ๋ฅด๋ชฌ์š”๋ฒ•์ด๋‚˜ ํ•ญ HER2 ์š”๋ฒ• ๊ฐ™์€ ๊ฐ ํ™˜์ž์— ๋”ฐ๋ฅธ ๋งž์ถค ์น˜๋ฃŒ ๊ฐ€ ๋ฐœ๋‹ฌํ•˜๋ฉด์„œ ํ˜ธ๋ฅด๋ชฌ์ˆ˜์šฉ์ฒด์™€ ์œ ๋ฐฉ์•”์˜ ๋ถ„์ž ์ƒ๋ฌผํ•™์  ํŠน์ง•์— ๋”ฐ๋ผ ํ™˜์ž์˜ ์ƒ์กด์œจ์˜ ๋ฐœ์ „ ์†๋„ ์ฐจ์ด์— ํž˜์ž…์—ˆ์„ ๊ฐ€๋Šฅ์„ฑ์ด ๋†’๋‹ค[19]. ์ด์™€ ๋”๋ถˆ์–ด ์›๊ฒฉ ์ „์ด๋œ ์žฅ๊ธฐ์— ๋”ฐ๋ผ์„œ๋„ ์‹œ๋Œ€์— ๋”ฐ๋ฅธ ์น˜๋ฃŒ ์„ฑ์ ์˜ ๋ฐœ์ „ ์†๋„์— ์ฐจ์ด๊ฐ€ ์žˆ๋‹ค๋Š” ๋ณด๊ณ ๊ฐ€ ์žˆ๋Š”๋ฐ, ์•„๋งˆ๋„ ์ด๊ฒƒ์ด ๋ณธ ์—ฐ๊ตฌ์—์„œ ํ์ „์ด ํ™˜์ž๊ฐ€ ์žฅ๊ธฐ ์ƒ์กด์œจ์ด ๋†’์•˜๋˜ ์ด์œ ์ผ ์ˆ˜ ์žˆ๋‹ค. Munich Cancer Registry์˜ 35๋…„๊ฐ„์˜ ์žฅ๊ธฐ ๋ณด๊ณ ์— ๋”ฐ๋ฅด๋ฉด ์น˜๋ฃŒ ๋ฐœ๋‹ฌ์— ์˜ํ•œ ํšจ๊ณผ๋Š” ๋ผˆ์ „์ด, ๊ฐ„์ „์ด, ๋‡Œ์ „์ด์— ๋น„ํ•˜์—ฌ ํ์ „์ด์—์„œ ๋‘๋“œ๋Ÿฌ์ง€๊ฒŒ ํ–ฅ์ƒ๋˜์—ˆ๋‹ค[20].
์ง€์†์ ์ธ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์„ ๋ฐ›๋Š” ํ™˜์ž๋“ค์—์„œ๋Š” ํ”ผ๋กœ, ์˜ค์‹ฌ, ๊ตฌํ† , ๊ณจ์ˆ˜์–ต์ œ, ์‹ ๊ฒฝ์—ผ, ํƒˆ๋ชจ์™€ ๊ฐ™์€ ๋ถ€์ž‘์šฉ์ด ๋ฐœ์ƒํ•˜๋Š” ๊ฒฝ์šฐ๊ฐ€ ๋งŽ๋‹ค[21,22]. ๋˜ํ•œ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์— ์˜ํ•œ ๋…์„ฑ ๋ฐœ์ƒ์ด ์‹ฌํ•œ ๊ฒฝ์šฐ์—๋Š” ํ™˜์ž์˜ ์ „์‹  ์ƒํƒœ ์•…ํ™”๋กœ ์ธํ•ด ์น˜๋ฃŒ๋ฅผ ์ค‘๋‹จํ•˜๊ฑฐ๋‚˜ ์•ฝ๋ฌผ์„ ๋ฐ”๊พธ์–ด์•ผ ํ•˜๋Š” ๊ฒฝ์šฐ๋„ ์žˆ๋‹ค. ๊ทธ๋ฆฌํ•˜์—ฌ ์ˆ˜์ˆ  ํ›„ ํƒ€ ์žฅ๊ธฐ ์ „์ด ๋ฐœ๊ฒฌ ํ›„ ์žฅ๊ธฐ ์•ˆ์ • ๋ณ‘๋ณ€์„ ๊ฐ€์ง„ ํ™˜์ž์™€์˜ ์ƒ๋‹ด์—์„œ ์น˜๋ฃŒ ๋˜๋Š” ๊ฒ€์‚ฌ๋ฅผ ์ค‘๋‹จํ•˜๊ธฐ๋ฅผ ์š”๊ตฌํ•˜๋Š” ๊ฒฝ์šฐ๊ฐ€ ๋งŽ๋‹ค. ํ•˜์ง€๋งŒ ์ด๋Ÿฌํ•œ ํ™˜์ž๋“ค์— ๋Œ€ํ•ด ์น˜๋ฃŒ๊ธฐ๊ฐ„์— ๋Œ€ํ•œ ์—ฐ๊ตฌ๊ฐ€ ๋ถ€์กฑํ•ด ๋ช…ํ™•ํ•œ ์น˜๋ฃŒ๊ธฐ๊ฐ„์— ๋Œ€ํ•œ ์ œ์‹œ๊ฐ€ ์–ด๋ ค์› ๋‹ค.
๋ณธ ์—ฐ๊ตฌ๋ฅผ ํ†ตํ•ด ์žฅ๊ธฐ๊ฐ„ ์•ˆ์ • ๋ณ‘๋ณ€์„ ์œ ์ง€ํ•œ ํ™˜์ž๊ตฐ์€ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด ์ „์ฒด ์ƒ์กด์œจ์ด ๋†’์Œ์„ ์•Œ ์ˆ˜ ์žˆ์—ˆ๊ณ , ๋˜ํ•œ ๋ณ‘์˜ ์ง„ํ–‰ ๊ฐ€๋Šฅ์„ฑ๋„ ์žˆ์œผ๋ฏ€๋กœ ์ถ”์ ๊ด€์ฐฐ ์‹œ ์žฅ๊ธฐ์ ์œผ๋กœ ์น˜๋ฃŒ์™€ ๊ฒ€์‚ฌ๊ฐ€ ํ•„์š”ํ•จ์„ ์„ค๋ช… ํ•  ์ˆ˜ ์žˆ๋‹ค๋Š” ์ ์—์„œ ๋ณธ ์—ฐ๊ตฌ์˜ ๊ฐ€์น˜๋Š” ํฌ๋‹ค๊ณ  ๋ณผ ์ˆ˜ ์žˆ๋‹ค.
๋ณธ ์—ฐ๊ตฌ์˜ ์ œํ•œ์ ์€ ํ›„ํ–ฅ์ ์ธ ์—ฐ๊ตฌ๋กœ ๋‹จ์ผ ๊ธฐ๊ด€์—์„œ ์‹œํ–‰๋˜์—ˆ๊ธฐ ๋•Œ๋ฌธ์— ๋Œ€์ƒ ํ™˜์ž์ˆ˜๊ฐ€ ๋งŽ์ง€ ์•Š๋‹ค๋Š” ๊ฒƒ์ด๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ์ด์™€ ๊ฐ™์ด ๋ฐœ์ƒ ๋นˆ๋„๊ฐ€ ๋†’์ง€ ์•Š์€ 2๋…„ ์ด์ƒ ์žฅ๊ธฐ ์•ˆ์ • ๋ณ‘๋ณ€์„ ๊ฐ€์ง€๋Š” ํ™˜์ž๋ฅผ ์ƒ๋Œ€์ ์œผ๋กœ ๊ธด ์ถ”์ ๊ด€์ฐฐ ๊ธฐ๊ฐ„์„ ๋ถ„์„ํ•˜์—ฌ ํŠน์„ฑ์„ ๋ณด๋Š”๋ฐ ์ž„์ƒ์  ์˜์˜๊ฐ€ ํฌ๋‹ค. ๋˜ ๋‹ค๋ฅธ ์ œํ•œ์ ์€ ์œ ๋ฐฉ์•” ์ „์ด ํ›„ ํ™˜์ž๋“ค์— ๋Œ€ํ•œ ์‚ถ์˜ ์งˆ ํ‰๊ฐ€๊ฐ€ ์ด๋ฃจ์–ด์ง€์ง€ ์•Š์•˜๋‹ค๋Š” ๊ฒƒ์ด๋‹ค. ์ด ๋˜ํ•œ ๋ณธ ์—ฐ๊ตฌ๊ฐ€ ํ›„ํ–ฅ์  ์ž๋ฃŒ ๋ถ„์„์œผ๋กœ ์ง„ํ–‰๋˜์—ˆ๊ธฐ ๋•Œ๋ฌธ์— ํ‰๊ฐ€๋˜์ง€ ์•Š์•˜๋˜ ํ•ญ๋ชฉ์— ๋Œ€ํ•œ ๋ถ„์„์ด ์ด๋ฃจ์–ด์งˆ ์ˆ˜ ์—†์—ˆ๋‹ค. ์ถ”ํ›„ ๋งŽ์€ ํ™˜์ž๋“ค์„ ๋Œ€์ƒ์œผ๋กœ ์ด์— ๋Œ€ํ•œ ์ „ํ–ฅ์  ์—ฐ๊ตฌ๊ฐ€ ํ•„์š”ํ•  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋œ๋‹ค.
๋ณธ ์—ฐ๊ตฌ์—์„œ ์ „์ด ๋ฐœ๊ฒฌ ํ›„ 2๋…„ ์ด์ƒ ์žฅ๊ธฐ๊ฐ„ ์•ˆ์ • ๋ณ‘๋ณ€์ด ์œ ์ง€ ๋˜์—ˆ์–ด๋„ ๊ทธ ์ดํ›„์—๋Š” ๋ณ‘์˜ ์ง„ํ–‰์ด ์ง€์†์ ์œผ๋กœ ๊ณ„์†๋˜์—ˆ๋‹ค. ์ด ํ™˜์ž๋“ค์˜ ์ „์ฒด ์ƒ์กด์œจ์€ ๋‹ค๋ฅธ ํ™˜์ž์— ๋น„ํ•˜์—ฌ ์ƒ๋Œ€์ ์œผ๋กœ ์ข‹์•˜์œผ๋‚˜ ์ง€์†์ ์ธ ์ถ”์ ๊ด€์ฐฐ๊ณผ ์—ฐ์†์ ์ธ ์น˜๋ฃŒ๊ฐ€ ์ง€์†๋˜์–ด์•ผ ํ•  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋œ๋‹ค.

ACKNOWLEDGMENTS

This study was supported by a grant of the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by Ministry of Science, ICT and Future Planning, Republic of Korea (1711045543/50462-2017).

Notes

The authors declare that they have no competing interests.

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Figureย 1.
Progression-free survival rate after distant metastasis.
jbd-5-1-1f1.tif
Figureย 2.
Overall survival rate after distant metastasis.
jbd-5-1-1f2.tif
Tableย 1.
Demographic and clinical information of the patients
Long-term stable disease group (n = 55) No. (%) Control group (n = 190) No. (%) p-value Long-term stable disease group (n = 55) No. (%) Control group (n = 190) No. (%) p-value
Age at diagnosis (yr)* 50.5 ยฑ 12.4 48.9 ยฑ 10.3 0.223 HR status
Breast operation โ€ƒPositive 46 (83.6) 117 (61.6) 0.002
โ€ƒBreast-conserving surgery 14 (25.5) 36 (18.9) 0.192 โ€ƒNegative 9 (16.4) 71 (37.4)
โ€ƒTotal mastectomy 41 (74.5) 154 (81.1) โ€ƒUnknown 0 2 (1.1)
T stage at diagnosis HER2 status
โ€ƒTis 1 (1.8) 0 0.320 โ€ƒPositive 20 (36.4) 66 (34.7) 0.386
โ€ƒT1 14 (25.5) 51 (36.8) โ€ƒNegative 32 (58.2) 122 (64.2)
โ€ƒT2 35 (63.6) 111 (58.4) โ€ƒUnknown 3 (5.5) 2 (1.1)
โ€ƒT3 3 (5.5) 17 (8.9) Subtype
โ€ƒT4 2 (3.6) 11 (5.8) โ€ƒHR+/HER2โ€“ 32 (58.2) 88 (46.3) 0.016
Nodal stage at diagnosis โ€ƒHR+/HER2+ 11 (20) 29 (15.3)
โ€ƒNegative 9 (16.4) 44 (23.2) 0.160 โ€ƒHRโ€“/HER2+ 8 (14.5) 37 (19.5)
โ€ƒPositive 46 (83.6) 141 (74.2) โ€ƒHRโ€“/HER2โ€“ 1 (1.8) 34 (17.9)
โ€ƒUnknown 0 5 (2.6) โ€ƒUnknown 3 (5.5) 2 (1.1)
M stage at diagnosis Ki-67
โ€ƒM0 42 (76.4) 164 (86.3) 0.060 โ€ƒNegative 20 (36.4) 95 (50) 0.560
โ€ƒM1 13 (23.6) 26 (13.7) โ€ƒPositive (โ‰ค 14%) 11 (20) 34 (17.9)
Histology โ€ƒPositive (> 14%) 11 (20) 52 (27.4)
โ€ƒDuctal carcinoma in situ 1 (1.8) 0 โ€ƒUnknown 13 (23.6) 9 (4.7)
โ€ƒInvasive lobular carcinoma 2 (3.6) 4 (2.1) Adjuvant chemotherapy
โ€ƒInvasive ductal carcinoma 52 (94.5) 186 (97.9) 0.141 โ€ƒDone 50 (90.9) 183 (96.3) 0.030
Histologic grade โ€ƒNot done 5 (9.1) 4 (2.1)
โ€ƒGrade 1 7 (12.7) 5 (2.6) 0.004 โ€ƒUnknown 0 3 (1.6)
โ€ƒGrade 2 21 (38.2) 72 (37.9) Adjuvant radiotherapy
โ€ƒGrade 3 18 (32.7) 89 (46.8) โ€ƒDone 29 (52.7) 100 (52.6) 0.370
โ€ƒUnknown 9 (16.4) 24 (12.6) โ€ƒNot done 25 (45.5) 74 (38.9)
Lymphatic invasion โ€ƒUnknown 1 (1.8) 16 (8.4)
โ€ƒPresent 29 (52.7) 118 (62.1) 0.130 Adjuvant hormonal therapy
โ€ƒNone 23 (41.8) 62 (32.6) โ€ƒDone 38 (69.1) 67 (35.3) < 0.001
โ€ƒUnknown 3 (5.5) 10 (5.3) โ€ƒNot done 8 (14.5) 63 (33.2)
Vascular invasion โ€ƒUnknown 9 (16.4) 60 (31.6)
โ€ƒPresent 6 (10.9) 23 (12.1) 0.495 Duration until metastasis from diagnosis (mo)
โ€ƒNone 47 (85.5) 157 (82.6) โ€ƒ> 24 30 (54.5) 81 (42.6) 0.080
โ€ƒUnknown 2 (3.6) 10 (5.3) โ€ƒโ‰ค 24 25 (45.5) 109 (57.4)

HER2=human epidermal growth factor receptor 2; HR=hormone receptor.

* Meanยฑ2SD.

Tableย 2.
Metastatic sites
Long-term stable disease group (n=55) No. (%) Control group (n=190) No. (%)
Bone 18 (32.7) 99 (52.1)
Lung 27 (49.1) 74 (38.9)
Liver 10 (18.2) 46 (24.2)
Brain 2 (3.6) 9 (4.7)
Pleura 1 (1.8) 18 (9.5)
Distant lymph nodes 7 (12.7) 28 (14.7)
Peritoneum 0 2 (1.1)
Tableย 3.
Factors affecting the survival rate of patients on univariate analysis
Survival (mo), meanยฑSD p-value
1st metastasis periods (mo) < 0.001
โ€ƒโ‰ค 24 81.5 ยฑ 4.2
โ€ƒ> 24 125.3 ยฑ 2.7
Period of treatment for longer periods (mo) < 0.001
โ€ƒโ‰ค 24 63.9 ยฑ 4.5
โ€ƒ> 24 118.3 ยฑ 3.2
Lymphatic invasion 0.005
โ€ƒPresent 85.9 ยฑ 4.5
โ€ƒNone 104.1 ยฑ 4.8
Hormonal status < 0.001
โ€ƒPositive 101.5 ยฑ 3.9
โ€ƒNegative 72.8 ยฑ 5.5
Nodal status 0.378
โ€ƒPositive 92.6 ยฑ 3.9
โ€ƒNegative 97.3 ยฑ 5.1
Histologic grade category 0.056
โ€ƒIII 83.1 ยฑ 5.1
โ€ƒI, II 99.6 ยฑ 4.9
HER2 status 0.520
โ€ƒPositive 88.6 ยฑ 4.1
โ€ƒNegative 96.8 ยฑ 5.6

HER2=human epidermal growth factor receptor 2.

Tableย 4.
Factors affecting the survival rate of patients on multivariate analysis
Hazard ratio (95% CI) p-value
1st metastasis period (โ‰ค 24 mo vs. > 24 mo) 6.862 (3.792-12.418) < 0.001
Period of treatment for longer periods (โ‰ค 24 mo vs. > 24 mo) 11.586 (3.589-37.399) < 0.001
Lymphatic invasion (present vs. none) 1.866 (1.026-3.401) 0.041
Hormonal receptor status (positive vs. negative) 0.682 (0.411-1.135) 0.141
Nodal status (positive vs. negative) 1.087 (0.576-2.049) 0.797

CI=confidence interval.

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