Surgery In Metastatic Breast Cancer Research Articles

Personalized surgical recommendations and quantitative therapeutic insights for patients with metastatic breast cancer: Insights from deep learning

AbstractBackgroundThe role of surgery in metastatic breast cancer (MBC) is currently controversial. Several novel statistical and deep learning (DL) methods promise to infer the suitability of surgery at the individual level.ObjectiveThe objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.MethodsWe introduced the deep survival regression with mixture effects (DSME), a semi‐parametric DL model integrating three causal inference methods. Six models were trained to make individualized treatment recommendations. Patients who received treatments in line with the DL models' recommendations were compared with those who underwent treatments divergent from the recommendations. Inverse probability weighting (IPW) was used to minimize bias. The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.ResultsIn total, 5269 female patients with MBC were included. DSME was an independent protective factor, outperforming other models in recommending surgery (IPW‐adjusted hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.19–0.78) and type of surgery (IPW‐adjusted HR = 0.66, 95% CI: 0.48–0.93). DSME was superior to other models and traditional guidelines, suggesting a higher proportion of patients benefiting from surgery, especially breast‐conserving surgery. The debiased effect of patient characteristics, including age, tumor size, metastatic sites, lymph node status, and breast cancer subtypes, on surgery decision was also quantified.ConclusionsOur findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed. This method can facilitate the development of efficient, reliable treatment recommendation systems and provide quantifiable evidence for decision‐making.

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database (NCDB)

PurposePrimary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer.MethodsThe National Cancer Database (NCDB, 2010–2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses.ResultsIn 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC who underwent lumpectomy had significantly higher positive margin rates (ILC 15.7% versus IDC 11.2%, p = 0.025). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden.ConclusionLobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.

Role of Surgery in Metastatic Breast Cancer: Insights from a Narrative Review.

Metastatic breast cancer is difficult to cure and has a worse prognosis with higher rates of mortality. Recently, breast surgery is believed to improve the survival rates among these women, but due to limited evidence, definite conclusions cannot be made. Therefore, we undertook this narrative review to synthesize the evidence from existing studies to assess the effectiveness of locoregional surgery and surgery of metastatic sites in improving the outcomes among women diagnosed with metastatic cancer disease along with the summary of current treatment guidelines. We reviewed PubMed and Embase and included both observational studies and randomized controlled trials (RCTs) that were published in English between 2000 and 2021. Outcomes were either survival, quality of life, toxicity related to local treatment assessed by mortality at the end of one month, progression-free survival, and breast cancer-specific survival. The main effect size assessed was hazard ratio with their 95% CIs. After literature search, we found 8 observational studies and 3 RCTs. The findings of the observational studies revealed that breast cancer surgery improves survival from 30% to 50% among women. However, findings from RCTs were mixed for local and distant progression survival. Surgery improved the local progression-free survival but worsened the distant progression-free survival. Besides, there was no effect of breast surgery on quality of life. Regarding the surgery of metastatic site, studies are complex with mixed findings and variation in survival depending upon the type of metastatic site and response to initial systematic therapy and other factors. Based on the existing mixed evidence, it is not possible to make firm and definite conclusions about the effectiveness of breast surgery in improving the survival or quality of life among women with metastatic breast cancer. In future, more RCTs are required with a larger sample size to confirm the findings of observational studies.

Development of a predictive model to identify patients most likely to benefit from surgery in metastatic breast cancer

Primary tumor resection for metastatic breast cancer (MBC) has demonstrated a survival advantage, however, not all patients with MBC benefit from surgery. The purpose of this study was to develop a predictive model to select patients with MBC who are most likely to benefit from surgery at the primary site. Data from patients with MBC were obtained from the Surveillance, Epidemiology and End Results (SEER) cohort and patients treated at the Yunnan Cancer Hospital. The patients from the SEER database were divided into surgery and non-surgery groups and a 1:1 propensity score matching (PSM) was used to balance baseline characteristics. We hypothesized that patients who underwent local resection of primary tumors had improved overall survival (OS) compared to those who did not undergo surgery. Based on the median OS time of the non-surgery group, patients from the surgery group were further categorized into beneficial and non-beneficial groups. Logistic regression analysis was performed to identify independent factors associated with improved survival in the surgery group and a nomogram was established using the most significant predictive factors. Finally, internal and external validation of the prognostic nomogram was also evaluated by concordance index (C-index) and using a calibration curve. A total of 7759 eligible patients with MBC were identified in the SEER cohort and 92 with MBC patients who underwent surgery at the Yunnan Cancer Hospital. Amongst the SEER cohort, 3199 (41.23%) patients received surgery of the primary tumor. After PSM, the OS between the surgery and non-surgery group was significantly different based on Kaplan–Meier survival analysis (46 vs. 31 months, P < 0.001), In the surgery group, 562 (55.20%) patients survived for longer than 31 months and were classified in the beneficial group. Significant differences were observed in patient characteristics between the beneficial and non-beneficial groups including age, grade, tumor size, liver metastasis, breast cancer subtype and marital status. These factors were used as independent predictors to create a nomogram. The internally and externally validated C-indices of the nomogram were 0.703 and 0.733, respectively, indicating strong consistency between the actual and predicted survival. A nomogram was developed and used to identify MBC patients who are most likely to benefit from primary tumor resection. This predictive model has the potential to improve clinical decision-making and should be considered routine clinical practice.

Abstract P2-14-16: Breast surgery for metastatic breast cancer: a Cochrane systematic review

Abstract Background Breast surgery is not standard treatment for metastatic disease, however several recent retrospective studies have suggested that breast surgery could increase survival. These studies have methodological limitations including selection bias. A systematic review mapping all randomized controlled trials addressing the benefits and potential harms of breast surgery is ideal to answer this question. Objectives To assess the effects of breast surgery on long term outcomes of women with metastatic breast cancer. Search methods We conducted searches using the MeSH terms ’breast neoplasms’, ’mastectomy’, and ’analysis, survival’ in the following databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed) and Embase (by OvidSP) on 08 December 2021. Selection criteria The inclusion criteria were randomized controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival, and toxicity from local therapy. Data collection and analysis Two review authors independently conducted trial selection, data extraction, and ’Risk of bias’ assessment (using Cochrane’s ’Risk of bias’ tool), which a third review author checked. We used the GRADE tool to assess the quality of the body of evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes and the hazard ratio (HR) for time-to-event outcomes. We calculated 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies. Main results We included four trials enrolling women with metastatic breast cancer in the review. These studies included 961 participants, 477 in the surgery group, and 485 in the control group. The evidence suggests that surgery does not improve overall survival as the quality of the evidence has been assessed as very low (HR 0.92, 95% CI 0.72 to 1.18; 4 studies; 961 women). The evidence suggests that surgery does not improve overall survival subgroup analysis according to the number of metastasis sites (HR 1.08, 95% CI 0.74 to 1.58; 3 studies, 320 women); bone metastasis only (HR 0.86, 95% CI 0.67 to 1.11; 3 studies, 253 women). According to the tumor subtype surgery seems not improve the overall survival in triple-negative (HR 1.10, 95% CI 0.53 to 2.28; 3 studies, 132 women) and HER 2 positive profile (HR 0.83, 95% CI 0.63 to 1.11; 3 studies, 262 women). However, for patients with luminal tumors surgery can significantly or marginally increase the survival (HR 0.81, 95% CI 0.67 to 0.98; 3 studies, 547 women). Breast surgery may improve local progression-free survival (HR 0.48, 95% CI 0.27 to 0.84; 3 studies; 686 women; low-quality evidence), while it does not change distant progression-free survival (HR 1.03, 95% CI 0,77 to 1.36; 3 studies; very low-quality evidence). Two studies reported quality of life outcomes, however it was not possible to perform a meta-analysis due to different tools used by these trials. Authors’ conclusions Based on existing evidence from four randomized clinical trials, breast surgery does not to improve overall survival for women with metastatic breast cancer. However, in subgroup analysis, women with luminal tumors present increase in survival. The quality of evidence was very low and the decision to perform breast surgery on these women should be individualized and discussed by a multidisciplinary team considering the potential risks, benefits, and costs of each intervention. Citation Format: Giuliano Tosello, Rachel Riera, Diego Christofaro, Crystian Oliveira, Marcelo Cruz, Thais R. Paulo, Bruna S. Mota. Breast surgery for metastatic breast cancer: a Cochrane systematic review. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-16.

Can We Use Artificial Intelligence Cluster Analysis to Identify Patients with Metastatic Breast Cancer to the Spine at Highest Risk of Postoperative Adverse Events?

Group patients who required open surgery for metastatic breast cancer to the spine by functional level and metastatic disease characteristics to identify factors that predispose to poor outcomes. A retrospective analysis included patients managed at 2 tertiary referral centers from 2008 to 2020. The primary outcome was a 90-day adverse event. A 2-step unsupervised cluster analysis stratified patients into cohorts using function at presentation, preoperative spine radiation, structural instability, epidural spinal cord compression (ESCC), neural deficits, and tumor location/hormone status. Comparisons were performed using χ2 test and one-way analysis of variance. Five patient "clusters" were identified. High function (HIGH) had thoracic metastases and an Eastern Cooperative Oncology Group (ECOG) score of 1.0±0.8. Low function/irradiated (LOW+RADS) had preoperative radiation and the lowest Karnofsky scores (56.0±10.6). Estrogen receptor or progesterone receptor (ER/PR) positive patients had >90% estrogen/progesterone positivity and moderate Karnofsky scores (74.0±11.5). Lumbar/noncompressive (NON-COMP) had the fewest patients with ESCC grade 2 or 3 epidural disease (42.1%, P < 0.001). Low function/neurologic deficits (LOW+NEURO) had ESCC grade 2 or 3 disease and neurologic deficits. Adverse event rates were 25.0% in the HIGH group, 73.3% in LOW+RADS, 24.0% in ER/PR, 31.6% in NON-COMP, and 60.0% in LOW+NEURO (P=0.003). Function at presentation, tumor hormone signature, radiation history, and epidural compression delineated postoperative trajectory. We believe our results can aid in expectation management and the identification of at-risk patients who may merit closer surveillance following surgical intervention.

Metastasectomy versus radiation of secondary sites in stage IV breast cancer.

1094 Background: Prospective trials have yielded mixed results on the utility of surgery in metastatic breast cancer (mBC). Thus far, however, studies have focused primarily on the impact of lumpectomy or mastectomy. We previously showed that a combined approach involving resection of primary and secondary sites (i.e. ‘metastasectomy’) in patients with limited mBC was associated with improved overall survival (OS). We sought to evaluate the effect on OS of two approaches to loco-regional therapy (LRT) at secondary sites: metastasectomy versus radiation therapy. Methods: This is a retrospective analysis of patients diagnosed with mBC from 2010-2017 using the National Cancer Database. We identified 5 cohorts of patients by site of metastasis: mBC involving only 1) bone, 2) brain, 3) liver, or 4) lung; and 5) patients with metastasis involving &gt;1 site. For each cohort, we used Kaplan-Meier (KM) models with log-rank testing to evaluate differences in OS, by the LRT approach at secondary sites (radiation versus metastasectomy). Prior to KM modeling, chi-squared statistics were used in each cohort to assess whether age, race, Charlson/Deyo score (CDS) for comorbidity, and receptor subtype were potential confounders of survival. The KM models were adjusted accordingly, as per the table below. Results: 53.4%) were between 50-70 years old, White (n=53,409, 78.9%), and had hormone receptor (HR)-positive/HER2 receptor-negative breast cancer. N=12,362 patients received radiation therapy at either the bone, brain, liver, or lung; while n=2674 underwent surgical resection of a metastatic site. Of patients with metastasis to 1 site (n=44,451), n=30,341(68.3%) involved the bone, n=1,119 (2.5%) involved the brain, n=5,227 (11.8%) involved the liver, and n=7,764 (17.5%) involved the lung. N=24,017 patients had metastatic disease involving &gt; 1 site. KM modeling revealed superior OS of patients undergoing metastasectomy versus radiation of secondary sites in all 5 cohorts (p&lt;0.05). The difference in median OS (ΔmOS) by LRT approach was more pronounced when metastasis involved only the liver (41.6 months) or lung (48.6 months), versus only the brain (9.7 months) or bone (8.7 months). Conclusions: Metastasectomy appears to confer a superior benefit for OS compared to radiation of secondary sites, particularly in patients with secondary site involvement limited to the liver or lung. More research is needed from prospective trials investigating surgical resection of metastatic sites.[Table: see text]

Results of ECOG-ACRIN E2108 Trial: Is This the End of Primary Surgery in Metastatic Breast Cancer?

Results of ECOG-ACRIN E2108 Trial: Is This the End of Primary Surgery in Metastatic Breast Cancer?

Locoregional Surgery in Metastatic Breast Cancer: Do Concomitant Metabolic Aspects Have a Role on the Management and Prognosis in this Setting?

Although they cannot be considered curative, the new therapeutic integrated advances in metastatic breast cancer (MBC) have substantially improved patient outcomes. Traditionally, surgery was confined to palliation of symptomatic or ulcerating lumps. Data suggest, in some cases, a possible additive role for more aggressive locoregional surgical therapy in combination with systemic treatments in the metastatic setting, although a low level of evidence has been shown in terms of improvement in overall survival in MBC patients treated with surgery and medical treatment compared to medical treatment alone. In this light, tumor heterogeneity remains a challenge. To effectively reshape the therapeutic approach to MBC, careful consideration of who is a good candidate for locoregional resection is paramount. The patient’s global health condition, impacting on cancer progression and morbidity and their associated molecular targets, have to be considered in treatment decision-making. In particular, more recently, research has been focused on the role of metabolic derangements, including the presence of metabolic syndrome, which represent well-known conditions related to breast cancer recurrence and distant metastasis and are, therefore, involved in the prognosis. In the present article, we focus on locoregional surgical strategies in MBC and whether concomitant metabolic derangements may have a role in prognosis.

Primary tumor removal improves the prognosis in patients with stage IV breast cancer: A population-based study (cohort study).

Adjuvant therapy including chemotherapy, hormonal therapy, and radiotherapy were often used as a common stereotypy for female stage IV breast cancer rather than surgery. This study aimed to define the role of local surgery in metastatic breast cancer. Female metastatic breast cancer patients were identified in the Surveillance, Epidemiology, and End Results (SEER) program data (2010-2013). We compared survival time between patients who received primary tumor removal (PTR) versus those who did not. Multivariate Cox regression models and competitive risk models were built to adjust potential confounders. Of 7669 female stage IV breast cancer patients, 2704 (35.3%) had surgery on their breast tumor and 4965 (64.7%) did not. In the entire cohort, women who underwent PTR had a 45% reduced risk of breast cancer-related death (multi-adjusted hazard ratio [HR], 0.55; 95% CI, 0.50 to 0.60) compared with women who did not undergo PTR (P<0.001). In a cause-specific hazard model (CS model), the multivariable HRs (95% CI) for the association of PTR with breast cancer related-death were 0.54 (0.50-0.60) in the multivariate-adjusted analysis. Similar results were also observed in the sub-distribution hazard function model (SD model) with corresponding multivariate HRs (95%CI) of 0.57 (0.52-0.63). Our study suggested that PTR was associated with improved survival in female stage IV breast cancer patients. The role of PTR in these patients needs to be re-evaluated.

Breast Reconstruction in the Setting of Stage 4 Breast Cancer: Is It Worthwhile?

The role of reconstruction after primary tumor surgery for metastatic breast cancer remains controversial. This report describes the outcomes for patients undergoing mastectomy with and without reconstruction in the setting of de novo stage 4 breast cancer. Using a prospectively maintained institutional breast surgery database, this study identified all patients who presented with de novo stage 4 breast cancer from January 2008 to December 2018. Patients were included if they had undergone mastectomy with or without reconstruction. Patient, surgical characteristics, and survival outcomes were abstracted and analyzed. The study identified 29 patients: 8 patients (28%) who underwent reconstruction (R) and 21 patients (72%) who did not (NR). Complete clinical response to induction systemic therapy was more frequent among patients in the R group than among those in the NR group for the primary disease (50% in R, 5% in NR), and to a lesser degree for distant disease (63% in R, 39% in NR). No difference in complication rates between the two groups was identified [n = 1 (13%) in R; n = 2 (10%) in NR; p = 1.0]. Overall survival from surgery was longer in the R group (100% at 2 and 5years) than in the NR group [85%; 95% confidence interval (CI), 68-100% at 2years vs 50%; 95% CI 27-91% at 5years] (p = 0.046). Breast reconstruction after mastectomy may be reasonable to consider for appropriately selected patients with de novo stage 4 breast cancer who have excellent responses to systemic therapy and anticipated durable survival.

Abstract P2-14-20: Early locoregional breast surgery improves overall and progression-free survival in oligometastatic breast cancer

Abstract Background Four percent of patients have Metastatic Breast Cancer (MBC) at the time of diagnosis. Surgery in this context is generally not recommended. However, tumour resection may have an effect on tumour load influencing metastatic growth. Some studies have suggested an advantage of locoregional surgery in MBC. The objective was to evaluate the effectiveness of surgery in the year following diagnosis of metastatic disease. Methods Data were collected within the ESME breast cancer data platform. Stage IV patients diagnosed between 2008 and 2014 without further personal cancer were included. Patients who died or progressed in 1-year post-diagnosis were excluded. We compared patients operated within the first 12 months after diagnosis with the others. Results Among 1977 patients with MBC at diagnosis, alive and progression-free at 12 months, 530 (26.8%) had surgery within this interval. Patients operated in the year of diagnosis had less oligometastatic disease (less than 3 metastases; 9.2% vs 21.8%, p&amp;lt;0.01) compared to patients with no surgery. They had less bone metastasis (57.7% vs 74.4%, p&amp;lt;0.01), more lymph node (33.2% vs 27.8%, p=0.02), lung (19.8%, p&amp;lt;0.01) and less liver metastasis (17.9% vs 26.8%, p&amp;lt;0.01) sites. Other treatments included more chemotherapy and HER2-targeted therapy (89.1% vs 69.6%, p&amp;lt;0.01), locoregional radiotherapy (81.7% vs 32.5%, p&amp;lt;0.01) and the same frequency of hormone therapy (79.8% vs 78.6%, p=0.57). Multivariate survival analysis based on Cox model showed that surgery of primary breast lesion performed within 12 months (Hazard Ratio(HR)=0.75, p&amp;lt;0.01), HER2 positive status (HR=0.42, p&amp;lt;0.01) and the non-visceral metastases (HR=0.80, p=0.02) improved overall survival (OS) whereas an older age than 50 (HR=1.50, p&amp;lt;0.01) and 3 or more metastases (HR=1.45, p&amp;lt;0.01) were associated with poorer survival. Progression-Free Survival (PFS) was also improved for locoregional surgery (HR=0.70, p&amp;lt;0.001) after adjustment on HER2 positive status (HR=0.70, p&amp;lt;0.01), age greater than 50 (HR=1.18, p&amp;lt;0.01) and 3 or more metastases (HR=1.27, p&amp;lt;0.01). Propensity score matching analyses confirmed these results. Discussion We demonstrated that surgery of primary breast lesion had a benefit on OS (HR=0.75, p&amp;lt;0.01), and PFS (HR=0.70, p&amp;lt;0.01) in metastatic patient. Metastasis number less than 3 was a complementary protective factor to surgery. Studies have sought to evaluate the population that could benefit from surgery of primary breast lesion in the event of metastatic disease. They showed an increasing morbimortality in plurimetastatic patients. In our study, patients with more than 3 metastases had poorer OS and PFS (HR=1.45, p=0.01 and HR=1.27, p=0.03 respectively). Conclusion Results of our study show that surgical control of primary breast lesion could be considered as an option in the locoregional treatment of MBC, particularly in non-visceral oligometastastic breast cancer. Citation Format: Hotton J, Lusque A, Rauch P, Leufflen L, Buhler J, Pierret M, Salleron J, Marchal F. Early locoregional breast surgery improves overall and progression-free survival in oligometastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-20.

Breast surgery for metastatic breast cancer.

Breast surgery for metastatic breast cancer.

Palliative radiotherapy (RT) to the breast using a novel hypofractionated radiotherapy regime: Results of the HYPORT phase I/II study (CTRI/2015/12/006407).

e12613Background: Trials of breast surgery in metastatic breast cancer (MBC) have failed to improve outcomes. RT to the breast could provide local palliation with a hypothetical benefit to progress...

Breast surgery for metastatic breast cancer.

Metastatic breast cancer is not a curable disease, but women with metastatic disease are living longer. Surgery to remove the primary tumour is associated with an increased survival in other types of metastatic cancer. Breast surgery is not standard treatment for metastatic disease, however several recent retrospective studies have suggested that breast surgery could increase the women's survival. These studies have methodological limitations including selection bias. A systematic review mapping all randomised controlled trials addressing the benefits and potential harms of breast surgery is ideal to answer this question. To assess the effects of breast surgery in women with metastatic breast cancer. We conducted searches using the MeSH terms 'breast neoplasms', 'mastectomy', and 'analysis, survival' in the following databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed) and Embase (by OvidSP) on 22 February 2016. We also searched ClinicalTrials.gov (22 February 2016) and the WHO International Clinical Trials Registry Platform (24 February 2016). We conducted an additional search in the American Society of Clinical Oncology (ASCO) conference proceedings in July 2016 that included reference checking, citation searching, and contacting study authors to identify additional studies. The inclusion criteria were randomised controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival, and toxicity from local therapy. Two review authors independently conducted trial selection, data extraction, and 'Risk of bias' assessment (using Cochrane's 'Risk of bias' tool), which a third review author checked. We used the GRADE tool to assess the quality of the body of evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes and the hazard ratio (HR) for time-to-event outcomes. We calculated 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies. We included two trials enrolling 624 women in the review. It is uncertain whether breast surgery improves overall survival as the quality of the evidence has been assessed as very low (HR 0.83, 95% CI 0.53 to 1.31; 2 studies; 624 women). The two studies did not report quality of life. Breast surgery may improve local progression-free survival (HR 0.22, 95% CI 0.08 to 0.57; 2 studies; 607 women; low-quality evidence), while it probably worsened distant progression-free survival (HR 1.42, 95% CI 1.08 to 1.86; 1 study; 350 women; moderate-quality evidence). The two included studies did not measure breast cancer-specific survival. Toxicity from local therapy was reported by 30-day mortality and did not appear to differ between the two groups (RR 0.99, 95% CI 0.14 to 6.90; 1 study; 274 women; low-quality evidence). Based on existing evidence from two randomised clinical trials, it is not possible to make definitive conclusions on the benefits and risks of breast surgery associated with systemic treatment for women diagnosed with metastatic breast cancer. Until the ongoing clinical trials are finalised, the decision to perform breast surgery in these women should be individualised and shared between the physician and the patient considering the potential risks, benefits, and costs of each intervention.

Cirugía y reconstrucción mamaria en el cáncer de mama metastásico, una aproximación a la situación en España mediante encuesta y revisión de la literatura

ObjectiveTo identify the current situation of locoregional surgery and breast reconstruction (BR) in patients with metastatic breast cancer (MBC) in Spain. MethodFrom April to September 2016, data were collected from an online survey sent to physicians involved in treating this group of patients. ResultsThere were 124 respondents: 46% plastic surgeons, 17.5% general surgeons, 30% gynecologists specialized in breast disease and 6.5% physicians from other specialties. A total of 47.5% of the respondents recommended locoregional surgery in MBC at the time of diagnosis. Eighty percent of respondents performed BR in MBC, of which 71.5% would consider it after a patient request. In patients not receiving radiotherapy, 84% of respondents chose immediate BR, 72.5% of them with a prosthesis. In irradiated patients, 77.5% of respondents preferred autologous reconstruction, 74.5% of them with latissimus dorsi myocutaneous flap. There were no differences between immediate BR or delayed-BR. Factors important in the decision to accept or refuse BR were a life expectancy of at least 2 years, the patient's comorbidities, tumor burden, response to systemic treatment, or more than 6 months of stable disease. The reasons for not performing BR were a poor prognosis and the risk of metastatic progression due to a temporary suspension of systemic treatment. ConclusionHalf of the respondents considered BR in a patient with MBC at diagnosis, assessing tumor burden, life expectancy, and stable disease. Protocols are required in this regard.

Significance of primary lesion resection in Stage IV breast cancer.

Systemic treatment with drugs is administered to prolong survival and palliate symptoms in Stage IV breast cancer patients who have distant metastases at diagnosis. Surgical procedures for the primary tumor are not actively recommended in guidelines due to lack of evidence indicating prognostic benefit. Recently, several retrospective studies have shown primary tumor resection to prolong overall survival in patients with Stage IV breast cancer. Prospective randomized trials began enrolling patients to examine this possibility and two have already reported results. However, the results of these two trials were discordant. The first trial, conducted in India, reported negative effects of primary tumor resection after primary systemic therapy. A Turkish trial then obtained a positive effect of surgery as primary treatment. Several questions regarding the effects, timing, methods and eligibility for primary surgery have yet to be answered. Robust evidence, which is anticipated from other ongoing trials examining surgery for metastatic breast cancer, is eagerly awaited.

Improved Survival After Primary Tumor Surgery in Metastatic Breast Cancer: A Propensity-adjusted, Population-based SEER Trend Analysis.

There is ongoing debate about nonpalliative primary tumor surgery in metastatic breast cancer patients. This issue has become even more relevant with the introduction of increasingly sensitive imaging modalities. Metastatic breast cancer patients were identified in the SEER registry between 1998 and 2009. The effect of primary tumor surgery on overall and cancer-specific mortality using risk-adjusted Cox proportional hazard regression modeling and stratified propensity score matching was assessed. Overall, 16,247 women with metastatic breast cancer were included. Of those 7600 women underwent primary tumor surgery although 8647 did not have any surgery at all. Primary tumor surgery decreased from 62.0% in 1998 to 39.1% in 2009 (P < 0.001). Primary tumor surgery was associated with decreased overall mortality (hazard ratio (HR) = 0.53, 95% CI 0.50-0.55, P < 0.001) and cancer-specific mortality (HR = 0.51, 95% CI 0.48-0.54, P < 0.001) in the propensity score-matched model. The benefit of primary tumor surgery increased from 1998 to 2009 for overall mortality (1998: HR = 0.72, 95% CI 0.59-0.89, 2009: HR = 0.42, 95% CI 0.35-0.50) and cancer-specific mortality (1998: HR = 0.72, 95% CI 0.58-0.89, 2009: HR = 0.40, 95% CI 0.33-0.48). The present study-the first population-based analysis using propensity score methods-provides evidence of a favorable impact of primary tumor surgery on mortality in metastatic breast cancer patients. Most importantly, the benefit of primary tumor surgery increased over time from 1998 to 2009. Although the final results of ongoing randomized studies are awaited, currently available evidence should be discussed with metastatic breast cancer patients.

Surgery for Stage IV Breast Cancer

Advances in systemic therapy have improved survival of womenwithmetastaticbreast cancer.TheThomaset al1 analysis of Surveillance,Epidemiology, andEndResults (SEER)data supports the concept that surgery may contribute to an outcome advantage by reducing the total body burden of disease.While this study’s overarching focus is indeedmeaningful, it is also informative to place results from this report in the context of conversations regarding breast cancer disparities associatedwith racial/ethnic identity, young age, and country of origin. First, lifetime incidence of breast cancer is lower for AfricanAmerican comparedwithwhiteAmericanwomen; therefore, African American women account for a smaller proportion of breast cancer cases compared with their general population distribution. Thomas and colleagues1 found a disproportionately high prevalence of AfricanAmericanwomen among their stage IV study population, and African Americanwomenwere also 30% less likely to undergo surgery. This treatment imbalance raisesquestions regardingselectionofpatients that are triaged toward more aggressive care. Interestingly, Park et al2 published a different analysis of SEER data, demonstrating that treatment variables are likely just as important asdisease stageand tumorbiology inexplainingbreast cancer survival improvements observed over the past several decades. Unfortunately, one can infer from these 2 SEERbased studies that inequities in the treatment offered to African American womenmay contribute to their disproportionately high breast cancer mortality risk. Second, breast cancer incidence increases with age; however, thebreastcancerburdenofyoung/premenopausalwomen generates substantial attention because of the associated impact on a population subset that assumesmuch of the nation’s family and general workforce responsibilities. Furthermore, while the population-based incidence rates of breast cancer in women younger than 45 years have been stable over the past severaldecades,weare indeedseeinga largernumberofyoung patients with breast cancer because census data confirm that this demographic has grown by nearly 10 million since 1980.3 Unfortunately, thepopulation-basedincidenceofstageIVbreast cancer has doubled among young Americanwomen4 but happily,Thomasetal1 foundthatyoungerwomenweremore likely to undergo surgery, and age younger than 45 years was an independent predictor of prolonged survival. Finally, regarding internationalpopulations,2phase3 trials comparing surgery vs no surgery in metastatic breast cancer were presented at the 2013 San Antonio Breast Cancer Symposium,with neither demonstrating a survival advantage associatedwith surgery.5 Unfortunately, both of the these studies are subject toquestions regarding their relevance in amore affluent country suchas theUnitedStates,wherepatientshave improved access to advanced diagnostic and treatment options. For example, the trial conducted in India did not includeanti-HER2/neutherapyandtheTurkish trialdidnotmandate biopsy of the metastatic focus. Both of these strategies are standard in the United States and influence survival. It is difficult (if not impossible) to identify anybreast cancer study that does not provide an opportunity to investigate disparities in disease burden and outcome.

Primary Surgery for Initial Metastatic Breast Cancer

The role of performing breast cancer primary surgery in patients with initial metastatic disease has been widely debated. To analyze potential survival