Locoregional therapy in luminal-like and HER2-enriched patients with de novo stage IV breast cancer

Abstract

BackgroundLocoregional therapy is rarely the standard of care for De Novo stage IV breast cancer but usually used for palliation of symptoms. This retrospective study aimed to determine whether surgery or radiation would contribute to survival benefit for this group of patients by examining the survival outcome through the disease molecular subtypes.Materials and methodsWe reviewed 246 patients with de novo stage IV (M1) breast cancer treated at our hospital between 1990 and 2009. Multivariable Cox Analysis was used to evaluate the survival association with subtypes and clinicopathologic factors.ResultsPatients with luminal-like subtype are mostly premonopausal (66.9%, P = 0.0002), with abnormal CA 15–3 level at initial diagnosis (58.7%, P = 0.01), a higher rate of bony metastases (78.5%, P = 0.02), and a lower rate of liver metastases (22.3%, P < 0.0001). Patients with HER2-enriched and triple negative showed higher rate of nuclear grade III, up to 35% and 40%, respectively (P = 0.01). There is no difference in treatment options patient received: systemic chemotherapy up to 82.2 ~ 95% (p = 0.0705), locoregional treatment up to 40.0 ~ 51.2% (P-0.2571). The median overall survival was 23.1 months: luminal-like subtype 39.6 months, HER2-enriched subtype 17.9 months, and triple negative subtype 13.3 months, respectively (P < 0.0001). In multivariate analysis, poor prognostic factors included HER2-enriched (HR 2.2, P < 0.0001) and triple negative subtype (HR 4.3, P < 0.0001), liver metastasis (HR 1.9, P < 0.0001), lung metastasis (HR 1.4, P = 0.0153), and bone metastasis (HR 1.8, P = 0.0007). Subgroup analysis revealed that local treatments (surgery or radiotherapy) to primary/regional tumors achieved better survival in patients with luminal-like (3-year survival 66.4% vs. 34.4%, p = 0.0001) and HER2-enriched (3-year survival 41.6% vs. 8.8%, p = 0.0012) subtypes, but not in triple negative subtype (P = 0.9575).ConclusionsFor better survival outcome, De Novo Stage IV breast cancer patients with luminal-like or HER2-enriched subtype should be offered local treatments when surgery and/or radiotherapy presents an option for proper control of the primary and regional tumors.

Is there a role for locoregional treatment of the primary tumor in de novo metastatic breast cancer in the era of tailored therapies?

“…The authors reported that surgery was not associated with improved OS in patients with TN tumors, whereas it was associated with improved survival in patients with either HR or HER2-positive tumors when hormonal therapy and trastuzumab were used. Results were confirmed in other studies for patients with HER2positive tumors who received trastuzumab, and for those with HR-positive tumors (60,69,70).…”

The survival benefits of local surgery in stage IV breast cancer are not affected by breast cancer subtypes: a population-based analysis

“…A study by Chen et al . found that local treatment including surgery or radiotherapy improved survival in patients with HR+/HER2- ( P = 0.0001) and HR±/HER2+ subtypes ( P = 0.0012), but survival did not improve in HR-/HER2- tumors after local treatment ( P = 0.9575) [ 19 ]. Neuman et al .…”

“…and Neuman et al . was only 45 and 35, respectively [ 19 , 20 ]. Therefore, we cannot conclusively establish the value of surgical intervention for HR-/HER2- patients.…”

“…An increasing number of studies have found that local treatment including surgery or radiotherapy significantly prolongs the survival in BC patients with de novo stage IV disease [ 12 – 18 ]. However, most of these studies spanned a long period of time, and the value of BCS in predicting the survival of patients treated with surgery is still limited [ 19 , 20 ]. In the current study, we performed a population-based analysis to evaluate the clinical value of local surgery of BC patients with de novo stage IV disease.…”

Establishing a predicted model to evaluate prognosis for initially diagnosed metastatic Her2-positive breast cancer patients and exploring the benefit from local surgery

“…We were supposed to estimate the degree of survival advantage from surgery and chemotherapy for diverse-risk prognostic patients, which was conducive to the individualization in the evaluation of therapeutic efficacy. Chen et al [ 28 ] performed a retrospective study to evaluate the potential benefit of local treatment in 246 stage IV BC patients and found that local surgery or radiotherapy prolonged OS for Her2-positive (3-year, 41.6% vs 8.8%, p = 0.001) and luminal-like (3-year, 66.4% vs 34.4%, p <0.001) BC patients. Recently, Pons-Tostivint et al [ 29 ] conducted a large-scale multicentric retrospective study of 4276 de novo MBC patients, which concluded that locoregional surgery of the primary tumor would improve OS, except for patients with triple-negative molecular subtype.…”