Surgical Resection of the Primary Tumor is Associated with Increased Long-Term Survival in Patients with Stage IV Breast Cancer after Controlling for Site of Metastasis

Background The benefit of surgical resection in patients presenting with metastatic breast cancer is not established. We hypothesized that surgical excision of primary tumors in patients with stage IV breast cancer would be associated with increased survival. Methods Chart review identified 409 patients with stage IV breast cancer treated from 1996 to 2005; 187 received surgical excision of their primary tumor and 222 did not. One hundred and two patients had bone-only metastases, 281 had metastases to other organs ± bone, and 26 had no metastases recorded. Patient characteristics were compared between groups using the chi-squared test. Cox regression models were used to calculate adjusted hazard ratios (aHR). The log-rank test compared the differences in survival between patients who did or did not undergo surgical resection. Results Mean age at diagnosis of all 409 patients was 57.8 ± 15.0 years. After controlling for age, comorbidity, tumor grade, histology, and sites of metastasis, patients who underwent surgical resection had longer median survival when compared with patients who did not undergo surgical resection (31.9 vs. 15.4 months, p < 0.0001; aHR 0.53 [95% CI 0.42-0.67]). Conclusions Surgical excision of the primary breast tumor was associated with significantly longer survival in this cohort of stage IV breast cancer patients, even after controlling for other factors associated with survival. Randomized clinical trials are needed to validate these findings.     

Effect of primary tumor resection on overall survival in patients with stage IV breast cancer

We aimed to evaluate the effect of primary tumor resection on overall survival in stage IV breast cancer patients. In total, 284 breast cancer patients presenting with breast cancer at stage IV at initial diagnosis, between 2001 and 2014, were enrolled in the study. Patients were divided into two groups based on surgical resection of the primary tumor. Overall survival (OS) between the two groups was analyzed. Patients in the surgery group (n = 92) had smaller tumors than those in the no‐surgery group (n = 192, T0‐1:17.7% vs 34.8%, P < 0.001). The surgery group more often had negative nodal status (5.7% vs 33.7%, P < 0.001). Multiple metastatic organ sites were more common in the no‐surgery group than in the surgery group (55.7% vs 15.2%, P < 0.001). The surgery group showed a better OS than the no‐surgery group (P = 0.01). Multivariate analysis showed that surgical resection of primary tumors tended to be associated with improved OS (HR = 0.67, P = 0.055). T stage, ER, HER2 and metastatic organ sites were independent prognostic factors for OS in multivariate analysis. Surgical resection of the primary tumor may be a treatment option for patients with stage IV disease and may not have a negative effect on overall survival.     

Primary tumor resection in patients with stage IV breast cancer: 10-year experience

The role of surgery in the management of stage IV breast cancer is controversial. Existing studies in Stage IV breast cancer have not closely evaluated the role of patient response to induction systemic therapy (IST) in its relationship to survival outcomes. We identified all patients with a diagnosis of de novo stage IV breast cancer who underwent surgery of their primary tumor from January 2008 to December 2018. Patients were grouped according to their response in the primary disease site into progression (progressive primary disease) or no progression (nonprogressive primary; comprising complete, partial and stable response). We identified a total of 45 stage IV breast cancer patients who underwent operative intervention of their primary breast tumor. Prior to surgical intervention, progression in the primary site during IST was identified in 13/42 patients (31%), of whom four patients also had progression in the distant disease. The 5-year survival was higher in the nonprogressive primary (74%) than the progressive primary disease group (52%) which did not reach statistical significance (p = 0.08). Age, pathologic tumor size, clinical nodal status, number of positive lymph nodes, and distant disease response to systemic therapy were significantly associated with survival. In this single institution experience, select patients with stage IV breast cancer at initial diagnosis who underwent resection of the primary tumor following systemic therapy achieved favorable overall and distant progression-free survival. Surgery is reasonable to consider for local palliation or in selected patients who have excellent response to systemic therapy and good performance status.     

Meta-Analysis to Determine if Surgical Resection of the Primary Tumour in the Setting of Stage IV Breast Cancer Impacts on Survival

Introduction

The role of primary tumor excision in patients with stage IV breast cancer is unclear. Therefore, a meta-analysis of relevant studies was performed to determine whether surgical excision of the primary tumor enhances oncological outcome in the setting of stage IV breast cancer.

Methods

A comprehensive search for relevant published trials that evaluated outcomes following excision of the primary tumor in stage IV breast cancer was performed using MEDLINE and available data were cross-referenced. Data were extracted following review of appropriate studies by authors. The primary outcome was overall survival following surgical removal of the primary tumor.

Results

Data from ten studies included 28,693 patients with stage IV disease of whom 52.8 % underwent excision of the primary carcinoma. Surgical excision of the primary tumor in the setting of stage IV breast cancer was associated with a superior survival at 3 years (40 % (surgery) versus 22 % (no surgery) (odds ratio 2.32, 95 % confidence interval 2.08–2.6, p < 0.01). Subgroup analyses for selection of patients for surgery or not, favored smaller primary tumors, less competing medical comorbidities and lower metastatic burden (p < 0.01). There was no statistical difference between the two groups regarding location of metastatic disease, grade of tumor, or receptor status.

Conclusions

Patients with stage IV disease undergoing surgical excision of the primary tumor achieve a superior survival rate then their nonsurgical counterparts. In the absence of robust evidence, this meta-analysis provides evidence base for primary resection in the setting of stage IV breast cancer for appropriately selected patients.     

Surgical conservation planning after neoadjuvant chemotherapy for stage II and operable stage III breast carcinoma

BACKGROUND: This study was performed to investigate the extent of tumor downstaging achieved in women with operable breast cancer treated with neoadjuvant chemotherapy and breast-conservation surgery, develop recommendations for effective surgical planning, and report local-regional recurrence rates with this approach. METHODS: One hundred nine patients with stage II or III (T3N1) breast cancer were treated in three prospective trials utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC, n = 72) or paclitaxel (n = 37) followed by segmental resection (n = 109) and axillary node dissection (n = 94). Postoperatively, patients received 4 additional cycles of FAC followed by irradiation of the breast. The median follow-up was 53 months. RESULTS: The median tumor size was 4 cm (range 1.1 to 9 cm) at presentation and only 1 cm (range 0 to 4.5 cm) after four cycles of chemotherapy. The primary tumor could not be palpated after chemotherapy in 55% of 104 patients presenting with a palpable mass and therefore required needle localization or ultrasound guidance for surgical resection. Of the 34 patients clinically deemed to have no residual carcinoma in the breast after chemotherapy and before surgery, only 50% of these patients were found to have no residual carcinoma on pathologic examination after surgery. Patients with primary tumors < or =2 cm were significantly more likely than patients with larger tumors to have complete eradication of the primary tumor prior to surgery (P <0.001). The 5-year local-regional recurrence rate was 5%. CONCLUSIONS: Tumor downstaging is marked in patients with operable breast cancer and requires close monitoring during chemotherapy. We recommend placement of metallic tumor markers when the primary tumor is < or =2 cm to facilitate adequate resection and pathologic processing. Resection of the tumor bed remains necessary in women deemed to have a complete clinical response to ensure low rates of recurrence.     

Surgical Removal of the Primary Tumor Increases Overall Survival in Patients With Metastatic Breast Cancer: Analysis of the 1988–2003 SEER Data

Background Primary treatments for stage IV breast cancer are chemotherapy and radiation, with surgery usually reserved for tumor-related complications. We sought to determine whether surgical removal of the primary tumor provides a survival advantage for women with metastatic breast cancer. Methods We conducted a retrospective, population-based cohort study by using the 1988–2003 Surveillance, Epidemiology, and End Results (SEER) program data. By use of multivariate Cox regression models, overall survival in women with stage IV disease was compared between women who underwent surgical excision of their breast tumor with women who did not, controlling for potential confounding demographic, tumor- and treatment-related variables, and propensity scores (accounting for variables associated with the likelihood of having surgery). Results Of 9734 SEER patients with stage IV breast cancer, 47% underwent breast cancer surgery and 53% did not. Median survival was longer for women who had surgery than for women who did not, both among women who were alive at the end of the study period (36.00 vs. 21.00 months; P < .001) and among women who had died during follow-up (18.00 vs. 7.00 months; P < .001). After controlling for potential confounding variables and propensity scores, patients who underwent surgery were less likely to die during the study period compared with women who did not undergo surgery (adjusted hazard ratio, .63, 95% confidence interval, .60–.66). Conclusions Analysis of the 1988–2003 SEER data indicated that extirpation of the primary breast tumor in patients with stage IV disease was associated with a marked reduction in risk of dying after controlling for variables associated with survival.     

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??Locoregional surgical strategies of stage IV breast cancer ZHAO Yan??ZHENG Xin-yu. Department of Breast Surgery, the First Affiliated Hospital, China Medical University, Shenyang 110001, China
Corresponding author: ZHENG Xin-yu?? E-mail: xyzheng@mail.cmu.edu.cn
Abstract Systemic therapy is the mainstream treatment of stage IV breast cancer. Current guidelines do not recommend locoregional surgery for Stage ?? breast cancer despite most retrospective studies suggesting a survival benefit. Surgical excision of the primary breast cancer tumor in the presence of synchronous metastatic disease is debated since limited prospective, randomized studies showing that surgical treatment of primary tumors in woman presenting with stage IV disease does not produce an increase in OS. However, the author suggests the situation could be treated individually, initial surgery could be done for those women requiring palliation of symptoms or with impending complications, such as skin ulceration, bleeding and pain if complete local clearance of tumor may be obtained and if other sites of disease are not immediately threatening to life, especially when it is offered in a multimodality treatment program and with the preference of patients.     

Ⅳ期乳腺癌局部外科治疗策略

综合治疗是Ⅳ期乳腺癌的主体治疗。尽管大多数回顾性研究提示切除原发病灶可以获得生存获益,然而,目前的指南并不推荐原发病灶的手术切除。现有有限的前瞻性临床研究并未发现总生存获益。所以,存在远处转移的原发病灶切除与否目前存在争议。然而,笔者建议应采用个体化治疗策略。对于那些需要缓解症状或即将出现并发症,如皮肤溃疡、出血和疼痛病人,如果手术能够保证肿瘤局部完全获得清除,而其他转移灶不会立即威胁生命,特别是在多学科讨论的基础上,并征询病人本人及家属的意愿,可以考虑行初始原发病灶姑息性手术切除。     

Does primary tumor resection improve outcomes for patients with incurable advanced breast cancer?

Background

Metastatic breast cancer (MBC) is considered incurable, and surgery has only limited benefit in the treatment of this disease. However, recent reports have indicated that primary tumor resection may improve patient outcomes. We retrospectively analyzed the surgical benefits and prognostic factors for patients with MBC who were treated at our center.

Methods

Ninety-two women, who had tumors of greater than 5 cm and distant metastasis at diagnosis, were included in this study. The effect of surgical treatment on survival was evaluated. Patient demographics and tumor characteristics were also investigated.

Results

Thirty-six patients had surgery for resection of primary tumors. There were no substantive differences between individuals, or between tumor characteristics, for patients who underwent surgery versus patients who did not. The median survival time for surgically treated patients was 25.0 months versus 24.8 months for patients who did not undergo surgical resection (P = 0.352). Only three patients relapsed within three months of surgery. For the remaining majority of patients, primary tumor resection gave some relief from the often severe symptoms that come from harboring a large tumor for an extended time. In univariate and subsequent multivariate analyses of predictive indicators, a diagnosis of triple-negative breast cancer and/or metastasis to more than three sites was significantly associated with a severe prognosis.

Conclusion

Primary tumor resection failed to prolong overall survival times in patients with incurable advanced breast cancer that was greater than 5 cm. However, surgery did improve the quality of life in patients who were expected to have a relatively long prognosis.     

Surgery of the Primary Tumor Offers Survival Benefits of Breast Cancer with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis

Background

Controversy exists around the locoregional management of the primary tumor for breast cancer associated with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM) due to the rarity of the disease and limited available data. This study aimed to compare outcomes of patients in the Surveillance, Epidemiology, and End Results (SEER) database with sISLM who underwent surgical resection and radiation of the primary tumor with those who did not.

Methods

This population-based retrospective study included breast cancer patients with sISLM without distant metastases from 2004 to 2016 in the SEER database. In this study, patients had been stratified by operative management, and propensity score matching (PSM) had been successfully applied.

Results

A total of 1172 breast cancer patients with sISLM were included in the study: 863 (73.6%) of patients underwent the primary tumor resection, and 309 (26.4%) patients did not undergo surgery. The median survival time in the surgery group was longer compared to the nonsurgery group in the overall cohort and the PSM cohort. We concluded that the primary tumor resection was associated with improved survival. Subgroup analysis further demonstrated that local surgery was not inferior to radical surgery.

Conclusion

For selected breast cancer patients with sISLM, surgery is a promising local intervention which may improve the survival.

     

Clinical and immunologic investigations of patients with urinary bladder tumors (author's transl)

Forty patients with urinary bladder tumors (26 cancer and 14 papilloma) were investigated by clinical and immunological methods. Patients with Stage I and II bladder cancer had a decrease in their delayed cutaneous hypersensitivity reactions in comparison to healthy controls. The same was found in patients with proliferating papillomas (WHO I) and benign papillomas. Patients with carcinoma in Stages III and IV had a reduced reactivity to recall antigens and could be immunized to a significantly lesser degree with primary antigens. In most cases a transurethral resection of the tumor was followed by radiotherapy. In four patients local immunotherapy was performed after resection of most of the tumor mass.     

Circulating Tumor Cells in Patients Undergoing Surgery for Primary Breast Cancer: Preliminary Results of a Pilot Study

Introduction  Circulating tumor cells (CTCs) have recently been shown to be an independent predictor of progression-free and overall survival in patients undergoing treatment for metastatic breast cancer. This study evaluates the presence and significance of CTCs in patient undergoing surgical resection of clinically localized primary breast cancer. Methods  Patients undergoing surgery for clinically localized primary breast cancer were enrolled into a prospective study. Thirty milliliters of blood was drawn and studied using the CellSearch assay. Results  Forty-one patients were enrolled at a single tertiary referral center. Ten patients (24.4%) had detectable CTCs preoperatively (PreOp). Nine (30%) patients were found to have CTCs postoperatively (PostOp). Overall, 16 (39%) were found to have CTCs either PreOp or PostOp. Hormone-negative patients were significantly more likely to have CTCs than hormone-positive patients. No other pathologic factor was predictive of the presence of CTCs. Conclusion  CTCs are detectable and quantifiable in breast surgery patients. CTCs were more likely to be found in hormone receptor negative patients. Further study will allow correlation with other pathological variables and clinical outcome.     

Pathologic Tumor Response of Invasive Lobular Carcinoma to Neo‐adjuvant Chemotherapy

Abstract: Neo‐adjuvant chemotherapy is used for locally advanced breast cancer patients with significant variation in tumor response. Our objective is to determine the clinicopathologic effect of neo‐adjuvant chemotherapy on invasive lobular carcinoma. A review of a single‐institution data base of women diagnosed with breast cancer identified 30 patients from 1999 to 2009 with operable invasive lobular carcinoma who received neo‐adjuvant chemotherapy. Patient demographics and clinicopathologic data were reviewed. Cases were reviewed by a single pathologist (NNE). Residual cancer burden class was determined for each case. Median patient age was 50 years (range 25–79). All tumors were hormone receptor positive and clinical stage II or III carcinomas. Most patients (53.3%) had combination anthracycline‐ and taxane‐based chemotherapy. Therapy‐related changes were noted within the tumor bed in 25 (83.3%) patients. Six (30%) of 20 patients with residual axillary disease had therapy‐related nodal changes. There were 11 patients with moderate residual disease (class II) and 18 (60%) with extensive (class III); there were no complete pathologic responses (class 0). Only one patient (3.3%) converted from mastectomy to breast‐conserving surgery. Four (13.3%) patients developed distant metastases; all had pleomorphic‐type, clinical stage III tumors with residual cancer burden III classification and developed distant disease in the 2 years after surgery (range 0–26 months). Median follow‐up time was 29.5 months (range 7–132). Patients with locally advanced pleomorphic‐type lobular carcinoma appear to develop early post‐treatment metastatic disease. Neo‐adjuvant chemotherapy did not appear to have significant impact on the surgical treatment of patients with invasive lobular carcinoma.     

Locoregional Resection in Stage IV breast cancer: tumor biology, molecular and clinical perspectives

The intact primary in patients diagnosed with Stage IV breast cancer is generally reserved for palliative indications. Haagensen and Stout's 1943 criteria of inoperability for carcinoma of the breast, including tumor fixation to the chest wall, ulceration, and peau d'orange, hold true. Surgery alone is unlikely to prolong life in such patients. Improvements in breast cancer screening and awareness mean fewer patients having inoperable breast cancer. The current problem is that imagining studies reveal some patients to have oligometastatic disease with an intact primary. This article considers surgical treatment as part of multimodal Stage IV breast cancer treatment for such patients. Several challenges to previous dogma to never operate on Stage IV breast cancer patients except with palliative intent have arisen.     

Effect of Primary Tumor Extirpation in Breast Cancer Patients Who Present With Stage IV Disease and an Intact Primary Tumor

Background Currently, therapy for breast cancer patients with stage IV disease and an intact primary tumor is metastasis directed; the primary tumor is treated only when it causes symptoms. A recent review suggested that surgery may improve long-term survival in such patients. We evaluated the effect of surgery in such patients on long-term survival and disease progression. Methods We reviewed the records of all breast cancer patients treated at our institution between 1997 and 2002 who presented with stage IV disease and an intact primary tumor. Information collected included demographics, tumor characteristics, site(s) of metastases, type/date of operation, use of radiotherapy, chemotherapy and hormonal therapy, disease progression (time to progression and location of progression) in the first year after diagnosis, and last follow-up. Overall and metastatic progression-free survival were compared between surgery and nonsurgery patients. Results Of 224 patients identified, 82 (37%) underwent surgical extirpation of the primary tumor (segmental mastectomy in 39 [48%] and mastectomy in 43 [52%]), and 142 (63%) were treated without surgery. The median follow-up time was 32.1 months. After adjustment for other covariates, surgery was associated with a trend toward improvement in overall survival (P = .12; relative risk, .50; 95% confidence interval, .21–1.19) and a significant improvement in metastatic progression-free survival (P = .0007; relative risk, .54; 95% confidence interval, .38–.77). Conclusions Removal of the intact primary tumor for breast cancer patients with synchronous stage IV disease is associated with improvement in metastatic progression-free survival. Prospective studies are needed to validate these findings. Presented in part at the Annual Meeting of the Society of Surgical Oncology, Atlanta, Georgia, March 3–6, 2005.     

Prognostic Factors for Metachronous Contralateral Breast Cancer: Implications for Management of the Contralateral Breast

The absolute number of breast cancer survivors who are at risk for metachronous contralateral breast cancer (mCBC) has dramatically increased. The objectives of this study were to identify factors predictive of survival for patients with mCBC and to determine clinicopathological factors predictive of advanced mCBC. Using the Surveillance, Epidemiology, and End Results data base, we identified women, ages 18–80, diagnosed with invasive breast cancer from 1992 to 2010. We excluded patients with bilateral and stage IV primary breast cancer. Patients who developed mCBC ≥12 months from initial diagnosis were identified. Kaplan–Meier methods and Cox proportional hazards modeling were used to determine survival of patients with mCBC. Multivariate logistic regression was utilized to determine factors associated with advanced mCBC. We identified 6,673 patients who developed mCBC during our study period. The median interval between initial breast cancer and mCBC was 5 years. The strongest predictor of overall survival was the nodal status of the mCBC. Other significant prognostic factors included patient age; race; size, nodal status, estrogen receptor status, grade, and type of surgery of the initial breast cancer; grade of the mCBC; and use of radiation therapy for the mCBC. Overall, 25% of mCBCs were node positive. Younger age, black race, and characteristics of the initial breast cancer (increased size, invasive lobular histology, mastectomy treatment, and node‐positivity) were significantly associated with node‐positive mCBC (all p < 0.0.05). The most powerful predictor of survival for patients with mCBC is the nodal status of mCBC. Patients with advanced initial breast cancers are more likely to develop node‐positive mCBC. Adherence to current surveillance and adjuvant therapy guidelines may minimize the risk and mortality of mCBCs.     

Matched Pair Analyses of Stage IV Breast Cancer with or Without Resection of Primary Breast Site

Background  Reports demonstrate improved survival of stage IV breast cancer patients with primary cancer resection. This may result from selection for surgery, rather than biological processes. Methods  We performed matched-pair analysis that minimized potential bias in selecting surgery for primary cancer. Chart review was also performed of 5-year survivors to assess selection bias affecting breast surgery. Results  19,464 breast cancer patients were identified; 808 (4.2%) were stage IV: 622 were analyzed after eliminating wrong diagnoses or staging, and limiting patients to Massachusetts residents. Matched-pair analysis narrowed or eliminated apparent survival benefit associated with primary site surgery in several comparisons. When the impact of the sequence of systemic and surgical treatments was studied in stage IV patients, 90% 2-year survival occurred in patients receiving chemotherapy first, in contrast to receiving chemotherapy simultaneously with or after surgery, suggesting selection for delayed surgery after excellent response to initial chemotherapy. In bone metastases, the 2-year survival advantage occurred with chemotherapy before surgery; no difference in survival with or without surgery occurred when these treatments were simultaneous. Among 5-year survivors, frequency of primary site surgery after excellent response to systemic therapy, breast surgery in stage III patients incorrectly classified as stage IV, and frequency of oligo metastases all indicated selection bias. Conclusions  Case selection bias in primary breast cancer resection in state IV patients may explain most, if not all, the apparent survival advantage of such surgery.     

Surgical Resection of Primary Tumors in Patients Who Present With Stage IV Colorectal Cancer: An Analysis of Surveillance,Epidemiology, and End Results Data, 1988 to 2000

Background Surgical resection of the primary tumor for patients who present with incurable stage IV colorectal cancer is controversial. National practice patterns have not been described. We evaluated the use of primary tumor resection in patients presenting with stage IV colorectal cancer.Methods Patients with stage IV colorectal cancer diagnosed between 1988 and 2000 were selected from the Surveillance, Epidemiology, and End Results database. Patients undergoing primary tumor resection were analyzed on the basis of sex, race, year of diagnosis, and the anatomical site of the primary tumor. We compared the survival of resected and nonresected patients.Results A total of 17,658 (66%) of the 26,754 patients presenting with stage IV colorectal cancer underwent primary tumor resection. Patients with resected disease were more likely to be young (mean age of 67.1 vs. 70.3 years) and to have right-sided tumors (75.3%, 73.0%, and 45.6%, respectively, for right, left, and rectal; P < .001). In all age groups, patients undergoing resection had higher median and 1-year survival rates (colon: 11 vs. 2 months, 45% vs. 12%, P < .001; rectum: 16 vs. 6 months, 59% vs. 25%, P < .001) when compared with patients who did not undergo resection.Conclusions Most patients who present with stage IV colorectal cancer undergo resection of the primary tumor. The proportion of patients undergoing resection depends on patient age and race and the anatomical location of the primary tumor. The degree to which case selection explains the treatment and survival differences observed is not known. Further investigation of the role of surgery in the management of incurable stage IV colorectal cancer is warranted.Presented at the 57th Annual Cancer Symposium of the Society of Surgical Oncology, New York, New York, March 18–21, 2004.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

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.