| Section One Therapeutic Strategy for Patients with Local Recurrence after Radical MastectomyResearch objective To explore the prognostic factors and therapeutic strategies for patients with local recurrence after radical mastectomy.Research methods Breast cancer patients admitted and treated in our hospital from January 1st,2003 to November 31 st,2015 were retrospectively analyzed.The inclusion and exclusion criteria were set up,and a total of 388 breast cancer patients with recurrence in either ipsilateral chest wall,or supraclavicular and infraclavicular regions,armpit or internal mammary lymphatic drainage region were screened.No distant metastasis was found in these patients through systemic examination,and the duration from local recurrence to distant metastasis was over 2 months.Clinicopathological data such as age(?35 years and >35 years),menstruation(menopause and premenopause),clinical classification(I,II and III),pathological type(non-invasive carcinoma,non-special invasive carcinoma and special invasive carcinoma),number of dissected lymph node(?10 and >10),lymph node metastasis(0,1-3 and ?4),ER,PR,Her-2,disease-free survival(DFS),site of local recurrence(chest wall,supraclavicular and infraclavicular regions,armpit,internal mammary region,and multiple regions),radiotherapy,chemotherapy,endocrine therapy,second operation,and survival were analyzed.Kaplan-Meier was adopted for survival analysis,while log-rank test was used for single factor analysis,and the Cox proportional hazard model was employed for multiple-factor analysis.Factors affecting the prognosis for patients with local recurrence were also analyzed.Meanwhile,the effects of different therapeutic means on the distant metastasis-free survival(DMFS)and overall survival(OS)of breast cancer patients with local recurrence after radical mastectomy were investigated.Research results The median age of all the 388 patients diagnosed with breast cancer was 44 years(range,21-78 years),while that of patients upon the diagnosis of local recurrence was 47 years(range,24-78 years).The median DFS was 17 months(range,1-255 months),the median follow-up period was 32 months(range,1-239 months),and the median duration from local recurrence to distant metastasis was 19 months(95%CI,17-25).Additionally,the median duration from local recurrence to death was 139 months(95%CI,89-NA),and a total of 89 patients died during the follow-up period,yielding the mortality of 22.93%.Findings in the current study suggested that the nonstandard surgery and radiotherapy might account for the important cause of local recurrence of breast cancer.None of our patients had received sentinel lymph node biopsy(SLNB)preoperatively,while 111 cases(28.61%)had the intraoperatively dissected lymph nodes of ?10,which might be the cause leading to local tumor recurrence.70 cases(18%)were pathologically confirmed to have ?4 metastatic armpit lymph nodes,but they did not receive adjuvant radiotherapy,which was also a factor resulting in local tumor recurrence.Additionally,19 cases(4.8%)had primary tumor at the diameter of >5cm and did not undergo postoperative adjuvant radiotherapy as required in the guideline,which was also one of the factors responsible for local tumor recurrence.208 out of the 388 patients had unresectable lesions,while the remaining 180 had resectable lesions,including 150(38.66%)preferring surgical resection and 30(12.61%)preferring drug therapy to reduce their classification before selective operation.Of these 180 patients,162 achieved negative incisal margin postoperatively(R0 resection),and 18 had residual disease under naked eye or microscope after surgery.Altogether 216 cases received local radiotherapy whereas the remaining 172 did not receive radiotherapy.Among the patients with surgically resectable local recurrence,the median DMFS in patients achieving R0(negative incisal margin)after surgery was remarkably superior to that in those with unresectable lesions(26.5 months Vs 13 months,Log-rank test,P<0.01).Among the patients with surgically resectable local recurrence,the median OS in patients achieving R0(negative incisal margin)after surgery was markedly better that in those with unresectable lesions(143 months Vs 70 months,Log-rank test,P<0.01).Patients with unresectable local recurrence received surgical treatment after systemic drug therapy to reduce their classification,and the difference in the median DMFS was not statistically significant compared with those preferring surgical treatment(40 months Vs 30 months,Log-rank test,P>0.05).Meanwhile,the difference in the OS showed no statistical significance compared with those preferring surgical treatment(90 months Vs NA Log-rank test,P>0.05).A total of 48 patients died after receiving radiotherapy upon the last follow-up,while 41 died in the non-radiotherapy group.In addition,the median survival in radiotherapy group was evidently better than that in non-radiotherapy group(39 months Vs 25 months,Log-rank test,P<0.05),revealing that radiotherapy could reduce the risk of death in patients with local recurrence.Differences in comprehensive treatment and single treatment among all patients were also compared.Typically,the comprehensive treatment referred to the sequential therapy among surgery,drug and radiotherapy,which was conducted in 232 cases.Single treatment suggested that only one therapeutic scheme was adopted;for instance,90 cases received drug therapy alone,and 60 received surgical treatment alone.The median DMFS in the comprehensive treatment group was longer than that in single treatment group,and the difference was statistically significant(27 months Vs 12 months,Log-rank test,P<0.01).Moreover,the OS in the comprehensive treatment group was outstandingly longer than that in single treatment group(NA Vs 70 months,Log-rank test,P<0.01).The variables with statistical significance in the single factor analyses above,as well as other important factors(age,ER,PR,Her-2,DFS,chemotherapy,radiotherapy,endocrine therapy and number of metastatic lymph node)were incorporated into the COX regression model for statistical analyses.The results indicated that,ER(?2=12.743,P=0.000),DFS(?2=174.009,P=0.000)and radiotherapy(?2=5.908,P=0.000)were the independent risk factors affecting the OS of patients with local recurrence,and the difference was statistically significant.DFS refers to the duration from the time of radical mastectomy after the initial diagnosis to the time of initial local recurrence.The survival of patient with a longer DFS is longer than even in the presence of local recurrence.Research conclusions For patients who are discovered local recurrence initially,with solitary lesion or small lesion range and negative postoperative incisal margin,surgical treatment should be selected as soon as possible.In addition,drug therapy can be selected to reduce their classification before resection if there is no surgery indication for the locally recurrent mass discovered initially.Difference in the DMFS is not statistically significant compared with that in those preferring surgical treatment.Surgery,radiotherapy and drug therapy exist as a synthesis during the entire therapeutic process,and single treatment means is included in the comprehensive treatment,either for sequential or combined treatment.Radiotherapy is the best therapeutic means to control the local disease,which can also reduce the risk of death in patients.All important factors are incorporated into the multi-factor analysis,which suggests that ER,radiotherapy and DFS are the independent risk factors affecting the OS of locally recurrent breast cancer.No uniform standard is available for the treatment of local recurrent after radical mastectomy at present;therefore,the selection or combination of surgery,radiotherapy,chemotherapy,endocrine therapy and targeted therapy should be further studied.Meanwhile,radiotherapy,the therapeutic means that can lower the mortality in patients with local recurrence,should be further discussed regarding its local scheme.Section Two Subgroup Analysis on the 110 Patients with Local Recurrence after R0 ResectionResearch objective To explore the optimal radiotherapy strategy for patients with local recurrence receiving R0 resection.Research methods Breast cancer patients admitted and treated in our hospital from January 1st,2003 to November 31 st,2015 were retrospectively analyzed.Meanwhile,the inclusion and exclusion criteria were set up.136 patients preferring surgical treatment with negative incisal margin were selected from the 388 patients with local recurrence.Among them,some patients did not have complete pathological data;as a result,only 110 cases with relatively complete pathological data were enrolled into the subgroup analysis.The therapeutic methods that the above patients received were analyzed.Kaplan-Meier was adopted for survival analysis,while log-rank test was used for single factor analysis,and the Cox proportional hazard model was employed for multiple-factor analysis.Factors affecting the prognosis for patients with local breast cancer recurrence were also analyzed,so as to explore the optimal therapeutic strategy for the 110 patients receiving R0 resection after local recurrence.All the 110 patients enrolled had local recurrence,including 84 with recurrence in the chest wall,12 with the supraclavicular and infraclavicular region metastasis,13 with armpit metastasis and 1 with chest wall and armpit metastases.Meanwhile,103 cases had single lesion,7 were not discovered multiple lesion;moreover,103 cases had the lesion diameter of ?2cm and 7 had that of >2cm.All lesions were surgically removed,which had reached the non-residue standard.After the second operation,66 cases(60%)received consolidation chemotherapy,42(38.18%)underwent consolidation endocrine therapy,and 74(67.27%)received consolidation radiotherapy.Besides,49 patients(44.54%)had local progression,with the median local progression time of 34 months(95%CI,25-42 months);36(32.73%)had distant metastasis,with the median distant metastasis time of 31 months(95%CI,25-38 months);13(11.81%)had local progression and distant metastasis;and 12(10.91%)had no tumor progression.In the single factor analysis of this group,74 patients received consolidation radiotherapy,and their median local progression time was remarkably better than that in those without radiotherapy,and the difference was statistically significant(40 months Vs 25 months,Log-rank test,P<0.01).Meanwhile,difference in the time of DMF between the radiotherapy group and the non-radiotherapy group was not statistically significant(Log-rank test,P>0.05).Difference in the OS between patients receiving consolidation radiotherapy and those without radiotherapy was not statistically significant(Log-rank test,P>0.05),which was inconsistent with the analysis results from the 388 patients with local recurrence after radical mastectomy.The possible reason was that the median distant metastasis time in the 388-patient group was 19 months,while that in the 110-patient group was 31 months.The 388-patient group consisted of more cases,with complicated conditions,which was likely to develop distant metastasis.Under such circumstances,systemic drug therapy rather than radiotherapy was preferred in clinical treatment in the case of distant metastasis.However,radiotherapy is a means for local treatment,which can screen patients benefiting from local treatment.In addition,the median distant metastasis time of radiotherapy is longer,along with relatively higher disease homogeneity;therefore,the obtained result that local radiotherapy did not benefit the OS was more accurate.Multi-factor analysis results.The variables with statistical significance in the single factor analyses above,as well as other important factors(age,ER,PR,Her-2,DFS,chemotherapy,radiotherapy,endocrine therapy and number of metastatic lymph node)were incorporated into the COX regression model for statistical analyses.The results indicated that,adjuvant endocrine therapy(?2=7.541,95%CI=27.1%-80.4%,P=0.006),DFS(?2=4.068,95%CI=101.4%-267%,P=0.043)and radiotherapy(?2=14.126,P=0.002,95%CI=21.7%-80.4%)were the independent risk factors affecting the LRR of patients with local recurrence after R0 resection,and the difference was statistically significant.Among patients with a second local recurrence in the involved regions(a new recurrent lesion in the involved site of the initial recurrence),the second recurrence rate in the chest wall was 42.35%(36/85),and the second local recurrence rate was as high as 60%(15/25)as a result of not receiving consolidation radiotherapy.Meanwhile,the second recurrence rate was 75%(3/4)for those receiving radiotherapy at the dose of <50Gy,while that for those receiving radiotherapy at the dose of ?50Gy and <60Gy was 35.7%(15/42),that for those at the dose of >60Gy was 27.27%(3/11),and patients receiving the dose of ?70Gy had no recurrence(0/3).The second recurrence rate in the involved supraclavicular and infraclavicular regions was 50%,and that in patients receiving no consolidation radiotherapy was as high as 85.71%.Meanwhile,the radiotherapy dose at 50Gy? dose< 60 Gy group had no recurrence(0/4),while that at >60Gy had no recurrence(0/1),and there was no group receiving the dose at <50Gy.The second recurrence rate in the involved armpit was 42.35%,and that in patients receiving no consolidation radiotherapy was as high as 44.44%.Meanwhile,the radiotherapy dose at 50Gy? dose< 60 Gy group had the second recurrence rate of 40%(2/5),and there was no group receiving other doses.Among patients with a second recurrence in the non-involved regions(a site that was not involved in the initial recurrence,but a new lesion occurred in the chest wall or lymphatic drainage region),the second recurrence rate in local chest wall was 22.22%(4/18).Among them,the second local recurrence rate was 25%(4/16)in those receiving no consolidation radiotherapy,no group received the radiotherapy dose at <50Gy,and the second recurrence rate in those receiving the radiotherapy dose at 50Gy? dose< 60 Gy was 0%(0/1).Besides,no patient received the radiotherapy dose at 60Gy? dose< 70 Gy,and the second recurrence rate in the ?70Gy group was 0%(0/3).The second recurrence rate in the non-involved supraclavicular and infraclavicular regions was 31.63%(31/98),and that in patients receiving no consolidation radiotherapy was as high as 41.53%(27/65).Meanwhile,no recurrence(0%,0/3)was observed in patients receiving the radiotherapy dose at <50Gy,the second recurrence rate in those receiving the radiotherapy dose at 50Gy? dose< 60 Gy was 17.39%(4/23),while that at 60Gy? dose<70Gy group was 0%(0/6),and that at ?70Gy group was also 0%(0/1).The second recurrence rate in the non-involved armpit was 13.54%(14/96),and that in patients receiving no consolidation radiotherapy was as high as 13.48%(12/89).Meanwhile,no patient receive radiotherapy at the dose of <50Gy,the second recurrence rate in those receiving the radiotherapy dose at 50Gy? dose< 60 Gy was 20%(1/5),while no patient received radiotherapy at the dose of 60Gy? dose<70Gy,and that at ?70Gy group was also 0%(0/1).The second recurrence rate in the non-involved internal mammary region was 2.72%(3/110),and that in patients receiving no consolidation radiotherapy was as high as 2.8%(3/107).Meanwhile,no patient receive radiotherapy at the dose of <50Gy,the second recurrence rate in those receiving the radiotherapy dose at 50Gy? dose< 60 Gy was 0%(0/2),while no patient received radiotherapy at the dose of 60Gy? dose<70Gy,and that at ?70Gy group was also 0%(0/1).Conclusions For patients with local breast cancer recurrence that receive second operation to totally resect the lesion,rescue radiotherapy can notably reduce the risk of local recurrence.In the meantime,whether the patients have adopted the rescue endocrine therapy,rescue radiotherapy and the length of DFS can markedly affect the second local recurrence.Nevertheless,no uniform standard is available regarding the selection of rescue scheme.Our results suggest that,the radiation dose of ?60Gy should be applied in the entire region covering the recurrence site,as well as the adjacent lymphatic drainage region,chest wall and supraclavicular and infraclavicular regions.Besides,small view or single-area radiation should be carried out for locally recurrent lesion after adjuvant radiotherapy. |
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