Long-term treatment efficacy in primary inflammatory breast cancer by hormonal receptor- and HER2-defined subtypes

Abstract

Background: Subtypes defined by hormonal receptor (HR) and HER2 status have not been well studied in inflammatory breast cancer (IBC). We characterized clinical parameters and long-term outcomes, and compared pathological complete response (pCR) rates by HR/HER2 subtype in a large IBC patient population. We also compared disease-free survival (DFS) and overall survival (OS) between IBC patients who received targeted therapies (anti-hormonal, anti-HER2) and those who did not.

Patients and methods: We retrospectively reviewed the records of patients diagnosed with IBC and treated at MD Anderson Cancer Center from January 1989 to January 2011. Of those, 527 patients had received neoadjuvant chemotherapy and had available information on estrogen receptor (ER), progesterone receptor (PR), and HER2 status. HR status was considered positive if either ER or PR status was positive. Using the Kaplan-Meier method, we estimated median DFS and OS durations from the time of definitive surgery. Using the Cox proportional hazards regression model, we determined the effect of prognostic factors on DFS and OS. Results were compared by subtype.

Results: The overall pCR rate in stage III IBC was 15.2%, with the HR-positive/HER2-negative subtype showing the lowest rate (7.5%) and the HR-negative/HER2-positive subtype, the highest (30.6%). The HR-negative, HER2-negative subtype (triple-negative breast cancer, TNBC) had the worst survival rate. HR-positive disease, irrespective of HER2 status, had poor prognosis that did not differ from that of the HR-negative/HER2-positive subtype with regard to OS or DFS. Achieving pCR, no evidence of vascular invasion, non-TNBC, adjuvant hormonal therapy, and radiotherapy were associated with longer DFS and OS.

Conclusions: Hormone receptor and HER2 molecular subtypes had limited predictive and prognostic power in our IBC population. All molecular subtypes of IBC had a poor prognosis. HR-positive status did not necessarily confer a good prognosis. For all IBC subtypes, novel, specific treatment strategies are needed in the neoadjuvant and adjuvant settings.

Keywords: HER2; breast neoplasm; hormonal receptor; inflammatory breast cancer; prognosis factor; subtype.

Figures

Figure 1.

Flow chart of patient population.

Figure 2.

(A) Survival by whether pCR was achieved. Kaplan–Meier estimates for patients who received neoadjuvant chemotherapy, underwent definitive surgery, and had evaluable status for ER, PR, and HER2. (B) Overall survival for each HR/HER2 subtype by whether pCR was achieved. Kaplan–Meier estimates for patients who received neoadjuvant chemotherapy, underwent definitive surgery, and had evaluable status for ER, PR, and HER2.

Figure 3.

DFS (left) and OS (right) for each HR/HER2 subtype Kaplan–Meier estimates for patients who received neoadjuvant chemotherapy, underwent definitive surgery, and had evaluable status for ER, PR, and HER2 with respect to OS and DFS in each subtype.