Primary tumor surgery for patients with stage IV HER2-positive breast cancer is associated with an improvement in overall survival (OS), according to results of a retrospective cohort review presented at the 2019 AACR Annual Meeting.
At a median follow-up of 21.2 months (range, 0-52), the median OS for patients who had surgery was 25 months compared with 18 months in those who did not undergo resection, leading to a 44% reduction in the risk of death (HR, 0.56; 95% CI, 0.40-0.77; P
“In the current era where HER2-targeted therapy has led to improved survival for HER2-positive metastatic breast cancer, our study suggests that surgery may be associated with even better survival for the HER2-positive stage IV breast cancer population,” said lead study author Ross Mudgway, a medical student at the University of California, Riverside School of Medicine. “Our results suggest that providers must consider patients individually when considering surgery and be aware that disparities in who receives surgery exist and should be addressed.”
Currently, there is no standard surgical treatment for patients with stage IV breast cancer, Mudgway said; this patient population typically receives systemic therapy, and radiation or surgery may occasionally be used for palliative care.
Prior data evaluating the survival benefit of primary breast cancer surgery have been mixed, he said, citing one phase III trial that demonstrated no benefit2
and another, the MF07-01 study,3
which showed that, with longer follow-up, there was an improvement in median survival with primary stage IV breast tumor resection.
With the advent of several systemic therapies that have significantly improved outcomes, such as trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), and ado-trastuzumab emtansine (T-DM1; Kadcyla), the impact of surgery in this current era of targeted treatments needs to be evaluated, Mudgway said.
In the retrospective cohort review, investigators analyzed data from 2.8 million breast cancers in the National Cancer Database between January 1, 2010, and December 31, 2012. After narrowing down for female patients, those with adenocarcinoma histology, invasive behavior, HER2 positivity, American Joint Committee on Cancer stage IV, exclusion of missing values, had a breast cancer diagnosis between 2010 to 2012, and reported surgery designation—the sum was a final sample of 3231 patients. The primary endpoints were receipt of surgery and OS.
The variables analyzed included age, race/ethnicity, insurance status, Charlson/Deyo score, treatment facility type, annual income, clinical tumor stage, clinical nodal stage, estrogen receptor (ER) status, progesterone receptor (PR) status, number of regional lymph nodes examined, radiation therapy, chemotherapy/immunotherapy (which was used as a surrogate for HER2-targeted therapy), endocrine therapy, site of metastasis, and vital status.
In the overall population (n = 3231), 71.3% of patients were white. More patients had private insurance (45.9%) than Medicare or other government insurance (31.7%), and 22.5% were not insured or on Medicaid. A total of 34.1% of patients were treated in an academic or research facility. Regarding annual income, 30.2% were of highest quartile and 19.2% were of the lowest. Seventy-five percent of patients had visceral metastases. For treatment, 31.8% had radiation, 89.4% had chemotherapy/immunotherapy, 37.7% had endocrine therapy, and 35% of patients underwent surgery.
Factors that attributed to increased likelihood of patients undergoing surgery included those with private insurance (42.3%; odds ratio [OR], 1.93; 95% CI, 1.53-2.42) or with Medicare/other government insurance (30.5%; OR, 1.36; 95% CI, 1.03-1.81). Additionally, patients of a lower income quartile were more likely to receive surgery (34.6%) than of those of the highest (34.4%; OR, 1.45; 95% CI, 1.12-1.87).
Patients who underwent radiation therapy were also more likely to have surgery (47.4%) than those who did not (28.8%; OR, 2.10; 95% CI, 1.76-2.51), as well as those who also received chemotherapy/immunotherapy versus not, at 36.5% and 22.2% (OR, 1.99; 95% CI, 1.47-2.70), respectively. Likewise, patients who received endocrine therapy were also more likely to undergo surgery (41.3%) compared with those who did not receive the treatment (31.3%; OR, 1.73; 95% CI, 1.40-2.14).
Some factors contributed to a decreased chance of patients with stage IV HER2-positive breast cancer undergoing surgery. Patients aged 20 to 39 years had a 44.5% likelihood, compared with 36.9% in those aged 40 to 59 years (OR, 0.75; 95% CI, 0.56-1.00) and 30.9% in those aged ≥60 years (OR, 0.58; 95% CI, 0.42-0.81). African-American patients were less likely (27.7%) compared with white patients (36.9%; OR, 0.68; 95% CI, 0.53-0.87), as were patients who were treated at an academic center (29.1%) versus a community practice (37.1%; OR, 0,67; 95% CI, 0.50-0.89).