Effects of locoregional radiotherapy in patients with metastatic breast cancer

ObjectivesThis study aims to assess the clinical outcomes of patients with metastatic breast cancer (MBC) who underwent local radiation therapy (RT) for the primary site.Material and methodsBetween 2005 and 2013, we retrospectively evaluated patients with MBC who received breast or chest wall RT with or without regional lymph node irradiation.Results2761 patients with breast cancer were treated with RT. Of them, 125 women with stage IV breast carcinoma were included. The median follow-up was 15 months (ranging from 3.8 to 168 months), when 54.7% of the patients had died; local progression was observed in 22.8% of the patients. The mean overall survival (OS) and local progression free survival (LoPFS) were 23.4 ± 2.4 months and 45.1 ± 2.9 months, respectively. Three- and five-year overall survival rates were, respectively, 21.2% and 13.3%. Local progression free survival was the same, 67.3%, at three and five years, respectively. Karnofsky Performance Status (KPS) (p = 0.015), number of metastatic sites (p = 0.031), RT dose (p = 0.0001) and hormone therapy (p = 0.0001) were confirmed as independent significant variables correlated with OS. The variables that were independently correlated with LoPFS were the number of previous chemotherapy lines (p = 0.038) and RT dose (p = 0.0001).ConclusionRT of the primary site in patients with MBC is well tolerated. The factors that presented positive impact on survival were good KPS, low disease burden (1–3 metastatic sites), and the use of hormone therapy.     

Predicting the survival benefit of local surgery in patients aged 70 years or older with stage IV breast cancer: A population-based analysis

PurposeThe aim of this study was to establish individualized nomograms to predict survival outcomes in older female patients with stage IV breast cancer who did or did not undergo local surgery, and to determine which patients could benefit from surgery.MethodsA total of 3,129 female patients with stage IV breast cancer aged ≥70 years between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results program. Multivariate Cox regression analysis was used to identify risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). Survival analysis was performed using the Kaplan–Meier plot and log-rank test. Nomograms and risk stratification models were constructed.ResultsPatients who underwent surgery had better OS (HR = 0.751, 95% CI [0.668–0.843], P < 0.001) and BCSS (HR = 0.713, 95% CI [0.627–0.810], P < 0.001) than patients who did not undergo surgery. Patients with human epidermal growth factor receptor 2-positive, lung or liver metastases may not benefit from surgery. In the stratification model, low-risk patients benefited from surgery (OS, HR = 0.688, 95% CI [0.568–0.833], P < 0.001; BCSS, HR = 0.632, 95% CI [0.509–0.784], P < 0.001), while patients in the high-risk group had similar outcomes (OS, HR = 0.920, 95% CI [0.709–1.193], P = 0.509; BCSS, HR = 0.953, 95% CI [0.713–1.275], P = 0.737).ConclusionOlder female patients with stage IV breast cancer who underwent surgery had better OS and BCSS than those who did not in each specific subgroup. Patients in low- or intermediate-risk group benefit from surgery while those in the high-risk group do not.     

Mastectomy and reconstruction in stage IV breast cancer: a survey of UK breast and plastic surgeons

The number of women with stage IV disease who have breast reconstruction is small. The primary aim of this study was to examine opinions as to the appropriateness of breast reconstruction in this group.The Association of Breast Surgeons (ABS) and the British Association of Plastic Reconstructive and Aesthetic Surgeons (BAPRAS) were invited to take part in an online survey.Of the respondents, 78.7% would operate on the primary tumour. Plastic surgeons showed a propensity for immediate reconstruction compared to their breast surgery colleagues, and 26.3% of breast surgeons would not offer reconstruction at all. Immediate latissimus dorsi (LD) flap and implant were the favoured method in early stage disease with delayed LD and implant the most popular option for stage IV disease.As survival figures continue to improve, the number of patients requesting reconstruction is likely to increase. Further debate will be necessary in anticipation of future service development.     

Low neighborhood socioeconomic status is associated with higher mortality and increased surgery utilization among metastatic breast cancer patients

PurposeLow socioeconomic status (SES) is associated with advanced stage, lower-quality care, and higher mortality among breast cancer patients. The purpose of this study is to examine the association between neighborhood SES (nSES), surgical management, and disease-specific mortality in de novo metastatic breast cancer (MBC) patients in the Surveillance, Epidemiology, and End Results (SEER) Program.MethodsMBC patients ages 18 to 85+ years diagnosed from 2010 through 2016 were identified in SEER. The cohort was divided into low, middle, and high nSES based on the NCI census tract-level index. Univariable and multivariable analyses were used to examine the relationship between nSES, surgery, and disease specific mortality in MBC patients.ResultsThere were 24,532 de novo MBC patients who met study criteria, with 28.7 % undergoing surgery. Over the study period, surgery utilization decreased across all nSES groups. However, lower nSES was associated with a higher odds of undergoing surgery (low OR 1.25 [1.15–1.36] p < 0.001; middle OR 1.09 [1.01–1.18] p = 0.022; ref high). Living in an area with lower SES was associated with a worse disease specific mortality (low HR 1.24 [1.25, 1.44; ], middle 1.20 [1.1–1.29]: ref high). Specifically, there was a 9.26 month mean survival differences between the lowest (41.02 ± 0.47 months) and highest (50.28 ± 0.47 months) nSES groups.ConclusionThese results suggest area of residence may contribute to differences in surgical management and clinical outcomes among de novo MBC patients. Future studies should examine the contributions of patient characteristics and preferences within the context of surgeon recommendations.     

Factors influencing outcome after surgery for stage IV colorectal cancer

PURPOSE: According to the classification system of the Japanese Society for Cancer of the Colon and Rectum, Stage IV colorectal cancer is characterized by distant metastasis, which is defined by four factors: liver metastasis (H factor), metastasis to organs other than the liver (M factor), peritoneal dissemination (P factor), and distant lymph node metastasis (N factor). We conducted this study to investigate the postsurgical prognosis of patients with Stage IV colorectal cancer (CRC), in reference to each of these four factors. METHODS: We analyzed the medical records of 73 patients who underwent surgery for Stage IV CRC at our hospital between 1991 and 2001. RESULTS: Univariate analysis revealed that P0 or P1 CRC (P < 0.001), absence of the M factor (P = 0.024), well or moderately differentiated adenocarcinoma (P < 0.001), resection of the primary tumor (P < 0.001), and curability B surgery (P < 0.0001) were associated with a better prognosis than other types of Stage IV CRC. Multivariate analysis revealed that tumor differentiation and surgical curability affected cancer-specific survival significantly. CONCLUSION: Surgery with curative intent should be considered for patients with Stage IV CRC defined by the P1 factor or H factor.     

Long-term survival after multimodality therapy including surgery for metastatic esophageal cancer

Background and objectives: Esophageal cancer (EC) remains an aggressive disease with a poor survival. Management of metastatic EC is limited to palliative chemotherapy (CT). Scientific contributions regarding the role of surgery are scarce and controversial. We analysed outcome of surgically treated metastatic EC patients.

Methods: We retrospectively identified surgically treated metastatic EC patients from our esophagectomy database. The aim of this study was to evaluate surgical complications, pathological response, oncological outcome and mean survival of these aggressively treated stage IV cancer patients.

Results: Twelve stage IV patients with disease presentation limited to outfield lymph node (LN) and/or liver metastasis were treated with an aggressive multimodality treatment including surgery. Mean age was 58 years (75% male, 75% Adenocarcinomas). Median postoperative hospital stay was 15 d. Radiological anastomotic leakage occurred in one patient. In hospital, mortality was nil. Complete resection was achieved in all but one. Metastatic recurrence occurred in 64% of R0 resected patients. At date of censoring, after a median follow-up of 22 months, 50% of the surgical resected patients are still alive and 33% are free of disease recurrence. Kaplan–Meier curves show a possibility to long-term survival after aggressive multimodality therapy including surgery.

Conclusions: In selected metastatic EC patients, multimodality treatment including surgery has an acceptable surgical outcome with a potentially long-term survival.     

Long-term follow-up of patients with metastatic breast cancer treated by trastuzumab: Impact of institutions

PurposeTrastuzumab in Human Epidermal growth Receptor 2-positive (HER2+) metastatic breast cancer (MBC) was established as standard therapy since 2001. The objective of this study was to search for significant prognostic factors in patients with HER2+ MBC treated by trastuzumab taking into account the institution where the treatment was given.Patients & methodsAll patients with HER2+ MBC treated by trastuzumab between 2001 and 2010 in the 8 hospitals of Franche Comte region were analysed. Univariate and multivariate analysis were conducted to search for factors related to overall survival (OS).ResultsAmong 1234 patients with MBC treated by chemotherapy between 2001 and 2010, 217 patients received trastuzumab. In this subset, the median age was 60 years, 8% and 38% had brain and liver metastases at first occurrence of MBC, 36% of, tumours were hormonal receptors positive. Patients were treated in 48% and 52% of cases in specialized and in general hospitals, respectively. The median OS length was 45.2 months (IQR 23.2–89.3 months). In univariate analysis the following factors were significantly related to favourable OS: inclusion in clinical trials, treatment in a specialized hospital, positive hormonal receptors status, age <50. In multivariate analysis remained significant: treatment in specialized hospital (aHR 0.78; 95%CI 0.64–0.94; p = 0.03) and age <50 (aHR 0.76; 95%CI 0.59–0.95; p = 0.02).ConclusionExposure to trastuzumab erases all established prognostic factors at the metastatic setting. The fact that patients treated in specialized hospitals presented a longer survival emphasizes the dramatic impact of this therapy and the relevance to optimize its use.     

影响乳腺癌患者保乳手术边缘阳性因素的临床研究

目的探讨乳腺癌的临床病理学特征对保乳手术边缘阳性的影响。方法189例预行保乳手术术(BCT)的原发性乳腺癌患者,分析她们的临床特征(年龄,活检类型)和病理学特征(肿瘤大小,组织学类型,激素受体状态,HER2状态,和腋窝淋巴结状态)与阳性手术边缘的关系。结果189例患者中本组室心针肿脾物案例活检确诊79例,门诊或手术中切除活检确诊128例。61例手术边缘阳性(32.3%)。结论本研究的结果揭示:肿瘤直径大于2cm,腋窝淋巴结阳性PR阳性和年龄小于50岁是乳癌保乳手术边缘阳性的高危因素对1999年1月～2004年7月189例乳腺癌患者按受保乳手术进行回顾性分析,并总结手术切口边保阳性与临床特征病理案组但表现及激素受体状态的关系。     

Surgery for stage IV gastric cancer

BACKGROUND: Surgical treatment for stage IV gastric cancer is controversial. METHODS: We analyzed the surgical experience with advanced gastric carcinoma in a tertiary referral center in Mexico City from 1995 through 2000. We analyzed surgical morbidity, mortality, and factors associated with prognosis. Survival was analyzed with the Kaplan-Meier method, and the curves were compared with the log-rank test. Significance was assigned at P <0.05. RESULTS: Seventy-six cases were identified. Mean patient age was 56 +/- 14.5 years. Thirty-nine patients (51.3%) were women. Patients were grouped according to surgical procedure: group 1 underwent resection (40 patients), group 2 underwent bypass procedures (10 patients), and group 3 underwent either celiotomy and biopsy alone or jejunostomy placement (26 patients). Twenty patients (26%) developed operative complications, but most were minor. There was no difference in morbidity between surgical groups and no difference according to patient's age. Operative mortality was 2.6%. Good palliation of symptoms was significantly more common in group 1 patients (82%) than in group 2 patients (60%) (P = 0.0001). Median survival was 8 months (95% confidence interval 4 to 12) for the entire cohort and 13, 5, and 3 months for groups 1, 2, and 3, respectively (P = 0.00001 for group 1 vs groups 2 and 3). CONCLUSIONS: Surgical resection for stage IV gastric cancer can be done with low operative mortality and acceptable morbidity rates, and it provides patients with good symptomatic relief. Advanced patient age is not a contraindication for surgical treatment.     

Factors associated with local breast cancer recurrence after lumpectomy alone

Background: The purpose was to determine the rate of local breast relapse in patients with breast cancer uniformly treated with partial mastectomy but without postoperative radiotherapy and without systemic adjuvant therapy. We also systematically examined the factors associated with local recurrence to determine whether a low-risk subgroup existed. Methods: A retrospective review of a prospectively followed (median, 8 years) cohort of 293 patients was performed. The end-point was ipsilateral local breast cancer recurrence. The patient's age, tumor size, nodal status, estrogen and progesterone receptor status, histology, and tumor and nuclear grade were studied, as were the presence and amount of carcinoma in situ and the presence of tumor emboli using univariate Kaplan-Meier and Cox step-wise multivariate analyses. Results: The overall local relapse rate was 26% (77 recurrences). Univariate factors significantly associated with decreased local relapse included older age, negative nodes, small tumor size, positive estrogen receptor status, and absence of tumor emboli. Significant multivariate variables were age, nodal status, estrogen receptor status, absence of comedo carcinoma in situ, and tumor emboli. A low-risk subgroup of 66 patients was defined with a 6% 10-year local recurrence rate. Conclusion: Important patient and tumor variables associated with local breast cancer relapse after breast-conserving surgery can define a low-risk subgroup.     

Factors associated with local breast cancer recurrence after lumpectomy alone: Postmenopausal patients

Background: We have been following a cohort of patients who underwent a lumpectomy without receiving adjuvant radiotherapy or adjuvant systemic therapy. We now report the experience of a postmenopausal subgroup. Methods: The postmenopausal subgroup included 244 patients accrued between 1977 and 1986 and followed up. The end point was ipsilateral local breast cancer recurrence. The factors studied were the patient’s age in years; tumor size (in mm); nodal status (N-, Nx, N+); estrogen and progesterone receptor status (<10, ≥10 fmol/mg protein); presence or absence of lymphovascular/perineural invasion; presence or absence, and type, of DCIS (none, non-comedo, comedo); percentage of DCIS; histological grade (1,2,3); and nuclear grade (1,2,3). Univariate analyses consisted of Kaplan-Meier plots and the Wilcoxon (Peto-Prentice) test statistic; the multivariate analyses were step-wise Cox and log-normal regressions. Results: The median follow-up of those patients still alive was 9.1 years, and the overall relapse rate was 24% (59/244). The univariate results indicated that the characteristics of smaller tumor size, negative nodes, positive ER status, and no lymphovascular or perineural invasion were associated with significantly (P<.05) lower relapse. From the multivariate analyses, the factors lymphovascular or perineural invasion, age, and amount of DCIS were all significantly associated with local relapse with both Cox and log-normal regressions. Additionally, there was weak evidence of an association between ER (P=.08 in the Cox regression and in the log-normal) and nodal status (P=.09 in the log-normal regression) with local relapse. We also are able to define a low-risk subgroup (N-, age ≥65, no comedo, ER positive, no emboli) with a crude 10-year local recurrence rate of 9%. Conclusion: With longer follow-up, and for postmenopausal patients, there continues to be support for the theory that local relapse is affected by the factors lymphovascular or perineural invasion, age, amount of DCIS, ER, and nodal status. A low risk subgroup has been identified. Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, March 16–19, 2000, New Orleans.     

Impact of age at diagnosis of metastatic breast cancer on overall survival in the real-life ESME metastatic breast cancer cohort

BackgroundYoung age is a poor prognostic factor in early stage breast cancer (BC) but its value is less established in metastatic BC (MBC). We evaluated the impact of age at MBC diagnosis on overall survival (OS) across three age groups (<40, 40 to 60 and > 60 years(y)).MethodsESME MBC database is a national cohort, collecting retrospective data from 18 participating French cancer centers between January 01, 2008 and December 31, 2014.ResultsAmong 14 403 women included, 1077 (7.5%), 6436 (44.7%) and 6890 (47.8%) pts were <40, 40–60 and > 60 y respectively. Pts <40 had significantly more aggressive presentations than other age groups: more frequent HER2+ (25.7 vs 15.3% in >60y) and triple negative subtypes (27.4 vs 14.6% in >60y), and more frequent visceral involvement (36.3 vs 29.8% in >60y). At a median follow-up of 48 months, median OS differed across age groups: 38.8, 38.4 and 35.6 months for pts <40, 40–60 and > 60y, respectively (p < 0.0001). Compared to pts <40y, older pts had a statistically significant higher risk of death (all causes of death included), although of limited clinical value (HR = 1.1, IC 95%:1.01–1.20). There was a significant trend for better OS in pts <40y with HER2+ and luminal diseases. A possible explanation is a greater use of anti-Her2 therapies as first-line treatments: 86.6, 81.9 and 74.9% for pts <40, 40–60 and > 60y, respectively (p < 0.0001).ConclusionAlthough young age seems associated with more aggressive presentations at diagnosis of MBC, it has no deleterious effect on OS in this large series.     

Role of surgery in the treatment of brain metastases in patients with breast cancer

Background: Patients whose brain metastases from breast cancer are treated nonsurgically have a median length of survival ranging from 2.5 to 7.5 months, and a median time to recurrence ranging from 2 to 5 months. Patients treated with radiotherapy have a median length of survival ranging from 3 to 4 months. Those treated with chemotherapy have a median length of survival ranging from 5.5 to 7.5 months. Methods: We conducted a retrospective analysis on 63 patients treated over a 10-year period. Only patients who underwent surgery for nonrecurrent brain metastases were studied. Sixty-one patients (97%) underwent surgery within 2 weeks of diagnosis of the brain metastases. Results: The median length of survival was 16 months (95% confidence interval [CI] 11 to 22 months), and the 5-year survival rate was 17% (CI 9% to 29%). Brain metastases recurred in 27 patients at a median interval of 15 months (CI 12 to 24 months). Eleven patients had local recurrence, 10 had distal recurrence, and seven developed leptomeningeal disease. Significant prognosticators of length of survival were age (p=0.011), menopause status (p=0.10), postoperative radiotherapy (p=0.054), preoperative neurologic status (p=0.011), and preoperative systemic disease status (p=0.0003). Systemic disease status had a significant effect on the length of survival but not on the time to recurrence. Presented at the 49th Annual Cancer Symposium of The Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

Radical resection of rectal cancer primary tumor provides effective local therapy in patients with stage IV disease

Background The optimal use of radical surgery to palliate primary rectal cancers presenting with synchronous distant metastases is poorly defined. We have reviewed stage IV rectal cancer patients to evaluate the effectiveness of radical surgery without radiation as local therapy. Methods Eighty stage IV patients with resectable primary rectal tumors treated with radical rectal surgery without radiotherapy were identified. Sixty-one (76%) patients received chemotherapy; response information was available for 34 patients. Results Radical resection was accomplished by low anterior resection (n=65), abdominoperineal resection (n=11), and Hartmann’s resection (n=4). Surgical complications were seen in 12 patients (15%), with 1 death and 4 reoperations. The local recurrence rate was 6% (n=5), with a median time to local recurrence of 14 months. Only one patient received pelvic radiotherapy as salvage treatment. One patient required subsequent diverting colostomy. Median survival was 25 months. On multivariate analysis, the extent of metastasis and response to chemotherapy were determinants of prolonged survival. Conclusions For patients who present with distant metastases and resectable primary rectal cancers, radical surgery without radiotherapy can provide durable local control with acceptable morbidity. The extent of metastatic disease and the response to chemotherapy are the major determinants of survival. Effective systemic chemotherapy should be given high priority in the treatment of stage IV rectal cancer.     

Costs associated with Eribulin treatment for patients with metastatic breast cancer in a comprehensive cancer center in France

BackgroundThere is no standard recommendation for metastatic breast cancer treatment (MBC) after two chemotherapy regimens. Eribulin (Halaven^®) has shown a significant improvement in overall survival (OS) in this setting. Its use may however be hampered by its cost, which is up to three times the cost of other standard drugs. We report the clinical outcomes and health care costs of a large series of consecutive MBC patients treated with Eribulin.MethodsA monocentric retrospective study was conducted at Institut Curie over 1 year (August 2012 to August 2013). Data from patient's medical records were extracted to estimate treatment and outcome patterns, and direct medical costs until the end of treatment were measured. Factors affecting cost variability were identified by multiple linear regressions and factors linked to OS by a multivariate Cox model.ResultsWe included 87 MBC patients. The median OS was 10.7 months (95%CI = 8.0–13.3). By multivariate Cox analysis, independent factors of poor prognosis were an Eastern Cooperative Oncology Group (ECOG) performance status of 3, a number of metastatic sites ≥ 4 and the need for hospitalization. Per-patient costs during whole treatment were €18,694 [CI 95%: 16,028–21,360], and €2581 [CI 95%: 2226–3038] per month. Eribulin administration contributed to 79% of per-patient costs.ConclusionsInnovative and expensive drugs often appear to be the main cost drivers in cancer treatment, particularly for MBC. There is an urgent need to assess clinical practice benefits.     

Skeletal metastases in 301 breast cancer patients:: Patient survival and complications after surgery

The aim was to identify prognostic variables associated with survival in 301 breast cancer patients after surgical treatment of skeletal metastases. The study period was 1986–2012. The median age at surgery was 61 (interquartile-range [IQR] 52–70) years. The cumulative 1-, 2-, and 5-year survival after surgery was 45% (95% CI 39–51), 27% (22–32), and 8% (5–12), respectively. The median follow-up time was 1 (IQR 0.2–2) year. Age over 60 years (Hazard ratio [HR] 1.9) and hemoglobin levels <110 g/L (HR 2) increased the risk of death after surgery. Patients with impending fractures (HR 0.4) had a lower death rate. The overall neurological function in patients with spinal metastases improved after surgery (p < 0.001). The complication rate was 25%, including 14% re-operations. Survival data and analysis of complications of this large cohort of surgically treated breast cancer patients help to set appropriate expectations for the patients, families, and medical staff.     

Radiotherapy omission after breast-conserving surgery is associated with reduced breast cancer-specific survival in elderly women with breast cancer

PURPOSE: To evaluate the effect of radiotherapy (RT) omission on survival in older breast cancer patients treated with breast-conserving surgery. METHODS: Data were analyzed for 4836 women aged 50 to 89 with T1-T2, N0-N1, M0 breast cancer. Tumor and treatment factors, relapse rates, and overall survival (OS) and breast cancer-specific survival (BCSS) were compared between women treated with and without RT in 3 age categories: 50 to 64 (n = 2398), 65 to 74 (n = 1665), and > or = 75 years (n = 773). RESULTS: Median follow-up was 7.5 years. Rates of RT omission significantly increased with advancing age (7%, 9%, and 26% in age 50-64, 65-74, and > or = 75 years respectively, P < .0001). RT omission was associated with significantly reduced local control, BCSS, and OS. Despite similar tumor characteristics and higher rates of systemic therapy use, women aged > or = 75 years were observed to have lower 5-year OS and BCSS when RT was omitted. CONCLUSION: These findings support the hypothesis that inadequate local therapy is associated with reduced survival in elderly women treated with breast-conserving therapy.