Abstract PS1-35: Combined primary site resection and metastasectomy in patients with metastatic breast cancer
Authors: Bilani Nadeem , Elson Leah , Liang Hong , Elimimian Elizabeth , Nahleh Zeina 
Published: February 2021

Background: We previously reported a significant survival benefit of surgery in patients with de novo stage IV breast cancer. However, prospective trials, focusing predominantly on the impact of lumpectomy or mastectomy in metastatic breast cancer (mBC) (versus metastatic resection, i.e. ‘metastasectomy’), have yielded inconclusive results. We sought to assess whether a combination of surgical approaches may be associated with optimal survival.

Methods: This is a retrospective analysis of patients diagnosed with mBC between 2004 and 2016 using the National Cancer Database. We identified a cohort of patients undergoing both primary site resection and metastasectomy, describing them using frequency and distribution statistics. Subsequently, we conducted a multivariate Cox regression survival model to understand whether this surgical approach was associated with better overall survival (OS) compared to patients undergoing lumpectomy/mastectomy alone, metastasectomy alone, or no surgery. This model controlled for relevant sociodemographic and clinicopathologic factors. Finally, we used the Kaplan-Meier method to demonstrate the utility of surgery in: 1) patients with mBC involving only 1 site, stratifying by tissue type as bone, brain liver, or lung and 2) patients with mBC involving &gt;1 site.

Results: A total of n=55,125 patients with mBC were included in this analysis. N=13,478 patients underwent lumpectomy/mastectomy alone, n=2116 underwent metastasectomy alone, n=912 underwent combined lumpectomy/mastectomy + metastasectomy, and n=38,619 did not undergo surgery. Of those that underwent combined resection, n=713 (78.2%) were White; n=132 (14.5%) were Black, and n=47 (5.2%) were Asian. Multivariate Cox regression survival modeling showed mBC patients undergoing combined resection exhibited the best OS (median OS: 50 months, HR 0.882, p=0.012) compared to patients undergoing lumpectomy/mastectomy alone (median OS: 43 months – reference category); while patients undergoing metastasectomy alone had worse OS (median OS: 30 months, HR 1.327, p&lt;0.0001), and those who did not undergo surgery had the worst OS (median OS: 21 months, HR 1.824, p&lt;0.0001). Kaplan-Meier modeling corroborated this survival benefit when mBC involved 1 site and when it involved multiple sites (log-rank p&lt;0.001). In further subgroup univariate analysis of patients with metastasis to 1 site, patients undergoing combined lumpectomy/mastectomy + metastasectomy exhibited superior survival compared to lumpectomy/mastectomy alone, when metastatic disease involved the liver or lung (log-rank p&lt;0.001), but not when it involved bone or the brain. Additionally, in patients with mBC involving only the lung, metastasectomy alone was also associated with a superior survival benefit to lumpectomy/mastectomy alone (log-rank p&lt;0.001), highlighting the potential impact of pulmonary metastasectomy.

Conclusions: Patients with newly-diagnosed mBC undergoing primary site resection in combination with metastasectomy exhibited longer survival compared to those undergoing only lumpectomy/mastectomy and those not undergoing surgery, particularly when metastasis involved only the liver or lung.

Table 1: Multivariate Cox regression model for overall survival in de novo stage IV patientsDe Novo Stage IV Patients (n=55,125)aVariableNo. (%)Median OS (95% CI)#HR (95%CI)p-valueSurgical approach&lt;0.0001Lumpectomy/mastectomy alone (ref)13,478 (24.4%)43 (42-44)1Metastasectomy alone2116 (3.8%)30 (28-32)1.327 (1.249-1.410)&lt;0.0001Lumpectomy/mastectomy + metastasectomy912 (1.7%)50 (45-54)0.882 (0.799-0.973)0.012No surgery38,619 (70.1%)21 (21-22)1.824 (1.774-1.875)&lt;0.0001Age&lt;0.0001&lt;50 (ref)10,057 (18.2%)39 (38-41)150-7029,437 (53.4%)29 (28-29)1.203 (1.166-1.242)&lt;0.0001&gt;7015,631 (28.4%)16 (15-17)1.623 (1.566-1.681)&lt;0.0001Race&lt;0.0001White (ref)40,128 (72.8%)27 (27-28)1Black9476 (17.2%)21 (21-22)1.097 (1.067-1.128)&lt;0.0001Hispanic3038 (5.5%)38 (36-40)0.733 (0.696-0.772)&lt;0.0001Asian1492 (2.7%)35 (33-38)0.812 (0.755-0.874)&lt;0.0001Other991 (1.8%)32 (28-36)0.805 (0.738-0.878)&lt;0.0001Charlson/Deyo comorbidity index&lt;0.00010 (ref)44,069 (79.9%)29 (29-30)117982 (14.5%)19 (18-20)1.274 (1.238-1.312)&lt;0.00012+661 (1.2%)11 (10-12)1.644 (1.576-1.715)&lt;0.0001Molecular subtype&lt;0.0001TNBC (ref)6721 (12.2%)12 (12-12)1HR+, HER2-27,905 (50.6%)32 (31-32)0.610 (0.588-0.632)&lt;0.0001HR-. HER2+4171 (7.6%)30 (28-31)0.556 (0.529-0.585)&lt;0.0001HR+, HER2+7394 (13.4%)40 (38-41)0.592 (0.566-0.619)&lt;0.0001Radiation therapy&lt;0.0001No (ref)36,848 (66.8%)24 (24-25)1Yes17,715 (32.1%)31 (31-32)1.036 (1.012-1.060)0.004Hormonal therapy&lt;0.0001No (ref)24,662 (44.7%)14 (14-15)1Yes28,635 (51.9%)37 (36-37)0.449 (0.438-0.462)&lt;0.0001Chemotherapy&lt;0.0001No (ref)25,360 (46.0%)21 (20-21)1Yes28,342 (51.4%)32 (31-32)0.632 (0.616-0.649)&lt;0.0001Immunotherapy&lt;0.0001No (ref)48,276 (87.6%)25 (25-25)1Yes6616 (12.0%)41 (40-43)0.668 (0.639-0.698)&lt;0.0001aNumber of cases with documented surgical status and survival data included in this model. #Median OS in months.

Citation Format: Nadeem Bilani, Leah Elson, Hong Liang, Elizabeth Elimimian, Zeina Nahleh. Combined primary site resection and metastasectomy in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-35.