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Treatment Outcome in Women with Operable HER 2-Positive Breast Cancer: A single Institutional Report

可開刀之人類上皮生長因子第二型接受器陽性乳癌患者之治療成效:單一機構之報告

摘要


目的:許多研究發現,賀癌平治療對人類上皮生長因子第二型接受器陽性之乳癌患者有幫助,但是增加腦部轉移之機會,我們報告我們機構以賀癌平治療可開刀之人類上皮生長因子第二型接受器陽性乳癌患者,其治療成效及治療失敗之表現;此外專注在中樞神經系統轉移之發行率及能預測有較高機會中樞神經系統轉移病人之因子。方法及材料:我們回朔性分析243位可開刀之人類上皮生長因子第二型接受器陽性之女姓乳癌患者,患者於2002年6月至2011年12月期間在我們醫院診斷及治療。所有病人之腫瘤皆大於2公分或者有淋巴轉移,且接受術後anthracycline為主之化學藥物治療合併或沒有接受賀癌平。跟據追蹤中出現之臨床症狀加上神經影像之檢查診斷中樞神經系統轉移。我們估算無事件存活率,整體存活率,以及無腦轉移存活率;並評估臨床及病理因子對預後之影響。我們也分析預測中樞神經系統轉移之因子。結果:經63.57個月的追蹤,整體之5年無事件存活率,整體存活率,及無腦轉移存活率分別為72%、85%和92%。60個事件中有43個是遠端轉移(71.7%),是治療失敗的主因。根據不同事件類型計算之5年累積發生率分別為:局部復發4.7%,中樞神經轉移2.57%,非中樞神經之遠端轉移15.83%,第二原發腫瘤1.46%,及非腫瘤引起之死亡0.4%。所有中樞神經轉移中,其中有6位是第一個治療失敗的地方,其中10位發生在其他轉移之後。未接受輔助性賀癌平治療,超過9顆淋巴結轉移,及真皮層侵犯在單一或多變數分析皆預測較差之無事件存活率(p=0.001, < 0.001, 0.042),這些因子同樣可預測整體存活率。無發現特別之因子可供預測以中樞神經轉移為第一表現之轉移(5年累積發生率在接受或未接受賀癌平之病人為1.86%及3.02%, p=0.633)。超過9顆淋巴結轉移,淋巴血管侵犯,及腫瘤分化等級較高會有較差之無腦轉移存活率(p= 0.043, < 0.001, < 0.001)。結論:使用輔助性賀癌平改善第二、三期具人類上皮生長因子第二型接受器陽性之乳癌患者之無事件存活率及整體存活率。我們的數據顯示使用輔助性賀癌平並未增加中樞神經轉移之機率。病人有超過9顆淋巴結轉移,淋巴血管侵犯,及腫瘤分化等級較高等因子可考慮於追蹤時加上腦部影像檢查。不過仍需更大型研究之數據來決定哪些病人是較容易發生中樞神經轉移。

並列摘要


Purpose: Women with HER-2 overexpressing breast carcinoma benefit from trastuzumab-based systemic therapy despite the awareness of increasing risk of brain failure from this treatment modality among several studies. We report the treatment outcome and patterns of failure in women with operable HER2-positive breast cancer using trastuzumab as adjuvant setting at our institution, furthermore, focus on the incidence of central nervous system failure and the predictors for those with high risk of developing CNS relapse. Method and Material: We retrospectively identified 243 women with HER2-positive operable breast cancer diagnosed and treated at our institution between June 2002 and December 2011. All patients with tumor size more than two centimeters or any positive lymph node received adjuvant anthracycline-based chemotherapy with or without trastuzumab. Central nervous system failure was recognized through clinical symptoms and neuro-images during follow up. We estimated the event - free survival (EFS), overall survival (OS), and brain-metastasis free survival (BMFS) using Kaplan-Meier method, and performed cox-proportional hazards models to assess the impact of clinical-pathologic parameters on EFS, OS. The covariates for predicting CNS relapse either as first site or as sequential event during follow up were also analyzed. Results: With median follow up of 63.57 months (range 8.8~132.4months) of entire cohort, the five year event-free survival rate, overall survival rate, and brain-metastasis free survival was 72%, 85%, and 92%, respectively. Forty-three of sixty first events (71.7%) were distal relapse which remained the main failure type of our cohort. The five year cumulative incidence of different first events, included loco-regional recurrence, CNS relapse, distal non-CNS relapse, second primary, and non-cancer death, were 4.7%, 2.57%, 15.83%, 1.46%, and 0.4%. Central nervous system failure either as first site of recurrence or as a sequential event was noted in six and ten women. No adjuvant trastuzumab, positive lymph node number more than nine, and dermis involvement significantly predicted poorer event free survival on uni-and-multivariate analysis(p= 0.001, < 0.001, 0.042, respectively). These factors also translated in predicting overall survival. No significant predictor was noted for the occurrence of CNS relapse as first site (5-year cumulative incidence: 1.86% and 3.02% in patients with or without adjuvant trastuzumab, p= 0.633). The negatively prognostic factors for brain-metastasis free survival were positive lymph node number more than nine, lymphovascular invasion, and high grade tumor (p= 0.043, <0.001, and <0.001, respectively). Conclusion: Using adjuvant trastuzumab improves event-free survival and overall survival in women with stage II /III HER2-positive breast cancer. The development of CNS relapse did not increase in our patients receiving trastuzumab based adjuvant therapy. Brain image as part of follow up might be considered, especially for those with positive lymph node number more than nine, high grade tumor, and with lymphovascular invasion. Larger prospective data or data from published randomized trials is needed for determining patients with high risks of developing CNS relapse.

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