| Background:Breast cancer is the most common invasive cancer and the leading cause of death from cancer among women worldwide.Patients younger than 35 years of age are relatively rare,accounting for 2%-4%of all cases diagnosed annually in the west but much more popular in Asia(10%-25%).Tumors in young women present with higher grade,higher T or N stage,lower differentiation,higher proliferation fraction and more vascular invasion.They also had a significantly higher portion of basal-like tumors and HER2riched tumors.It is believed breast cancer at a young age is associated with more aggressive biological behavior and worse prognosis than in elderly,characterized by higher incidence of recurrence and higher risk of death,even treated with more aggressive therapies.However,few studies have investigated on survival outcomes after patients develop locoregional relapse or distant metastasis.This study was to investigate the recurrence pattern and subsequent survival outcomes in young breast cancer patients when compared with elderly patients.Methods:Breast cancer patients who received mastectomy or breast-conserving surgery from January 2008 to December 2012 were included in this study.Respectively,483 patients were≤35 years old and 739 patients were≥65 years old.Comparison was made between young and elderly groups concerning the baseline characteristics,diseasefree survival,overall survival,recurrence pattern and survival after recurrence.Cox regression models were utilized to determine the predictive value of multiple factors in outcomes of patients.Results:Comparing with elderly,the young population presented with a higher rate of pathologic tumor stage,positive pathologic lymph node,grade III tumors,and lymphovascular invasion.After a median follow-up of 56.5 months,patients in the young population had a significantly lower 5-year disease-free survival(73.7%vs 83.4%,P=0.001),while no difference in 5-year overall survival was observed(91.7%vs 91.7%,P=0.721).In addition,the 5-year cumulative incidences of locoregional relapse(8.9%vs 4.3%,P=0.009)and distant metastasis(18.8%vs 9.5%,P<0.001)were significantly higher in the young patients.However,in patients with distant metastasis,the survival outcomes were significantly better in the young patients(5-year overall survival:60.0%vs 47.3%,median:70.9 vs 49.4 months,P=0.025;5-year survival after recurrence:31.0%vs 24.3%,median:38.8 vs 12.1 months,P=0.001).There was no difference in patients with locoregional relapse.Conclusions:Young breast cancer patients present with more aggressive clinicopathological features and have poor prognosis compared with elderly.Although they were at a higher risk to develop locoregional relapse and distant metastasis after surgery,patients with distant metastasis might have better survival outcomes.Background:Breast cancer is the most common malignancy in women,and the leading cause of death from cancer among women worldwide.Women with breast cancer that overexpresses human epidermal growth factor receptor 2(HER2)are at greater risk for disease progression and death.Trastuzumab has been recommended to block HER2 signaling pathway in order to improve the outcome of this cancer.However,metastatic breast cancer eventually develops resistance to trastuzumab.Allitinib is an orally active small molecule that inhibits the tyrosine kinases of HER1/HER2/HER4.In phase Ia clinical trial,we explored the safety and tolerability of allitinib in solid tumors.This study was conducted to evaluate the tolerability,pharmacokinetics,and preliminary efficacy of allitinib plus capecitabine in advanced HER2 positive breast cancer.Methods:This study was a single-center,single-arm,and open-label clinical trial,and enrolled advanced HER2 positive breast cancer.It was a 3+3 dose-escalation study composed of two parts.Allitinib was taken once in the single-drug phase and then combination of allitinib 300mg,or 400mg,or 600mg,or 800mg,three times per day,dayl21,plus capecitabine 2000mg/m2/day,day1-14,repeated every 21 days,was continued.The primary end points were safety and tolerability,and the secondary end points were pharmacokinetics,overall response rate and progression free survival.Results:From March 2015 to April 2016,22 patients were enrolled in this study.The combination of allitinib 400mg three times per day,day 1-21,plus capecitabine 2000mg/m2/day,day1-14,repeated every 21 days,was defined as the maximum tolerated dose.Dose-limiting toxicity was grade III diarrhea which could not be controlled by drugs.In the single-drug phase,concentration of allitinib increased gradually,reached peak at 34 hours,and then decreased to baseline after 12 hours.In the combination phase,area under the curve of allitinib concentration reached peak in the first day,and then decreased to stable level.The most common treatment related adverse events were diarrhea(95.5%),nausea(50.0%),loss of appetite(36.4%),glutamic-pyruvic transaminase elevation(54.5%),glutamic-oxalacetic transaminase elevation(50.0%),bilirubin elevation(81.8%),leukopenia(50.5%),neutropenia(45.5%),and hypokalemia(45.5%).The overall response rate and clinical benefit rate were 41%and 73%,respectively.With a median followingup of 14 months,the median progression free survival was 7.1 months,and the median overall survival was not reached.Conclusions:Combination of allitinib and capecitabine was well tolerated and showed preliminary efficacy in the treatment of metastatic HER2 positive breast cancer,but special attention should be paid to the adverse event of diarrhea.The recommended dosage of phase Ⅱ clinical trial was the combination of allitinib 400mg three times per day,day1-21,plus capecitabine 2000mg/m2/day,day 1-14,repeated every 21 days. |
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