Abstract P3-10-05: Response to neoadjuvant systemic therapy (NST) in inflammatory breast cancer (IBC) according to estrogen receptor (ER) and HER2 expression.
Authors: Masuda H , Iwamoto T , Brewer T , Hsu L , Kai K , Woodward WA , Reuben JM , Valero V , Alvarez RH , Willey J , Hortobagyi GN , Ueno NT 
Published: August 2014

Background: Inflammatory breast cancer (IBC) is the most aggressive form breast cancer. NST, followed by local therapy (surgery and radiation therapy), is considered the current standard therapy for IBC. Among noninflammatory breast cancers, sensitivity to NST differs based on ER and HER2 status. However, whether the sensitivity to NST also differs in primary IBC based on ER status or other prognostic factors has not been studied in a large cohort.

Methods: We retrospectively reviewed 1078 patients (pts) newly diagnosed with IBC from April 1989 to January 2011. Of these, 838 pts met our inclusion criterion of stage III disease at diagnosis, and 713 of these pts had received NST and surgery. Among this population, 545 pts had information available on both ER and HER2 status. We compared pathological complete response (pCR) rates (defined as no evidence of invasive disease in the breast and ipsilateral axillary limph nodes) and clinical characteristics between ER and HER2-status subgroups and analyzed their clinical outcome. We used the Kaplan-Meier method to estimate the median recurrence-free survival (RFS) after surgery and overall survival (OS), and the Cox proportional hazards regression model to test the statistical significance of potential prognostic factors in each group.

Results: Overall 177 pts had ER+HER2− tumors; 75, ER+HER2+; 134, ER-HER2+; and 159, ER-HER2−. NST consisted of anthracycline-based [A] alone, a taxane [T] alone or with A+T; HER2 targeting therapies (H) were administered to 117 patients with HER2-positive breast cancer after 1998. Overall pCR rate was 14.7%. pCR rates are shown by marker subtype and NST received in the table below. pCR rate, nuclear grade, vascular invasion, clinical response to NST, adjuvant treatment, radiation therapy, and adjuvant hormonal therapy differed significantly among subgroups.

The median RFS and OS for all patients was 19.2 and 33.2 months, respectively. In multivariate analysis, BMI, ER status, lymphatic invasion, radiation therapy, and pCR rate were associated with RFS, and ER status, vascular invasion, radiation therapy, and pCR rate were associated with OS. Except in the ER+HER2− group, pCR was associated with better prognosis compared to non-pCR. Adjuvant hormonal therapy improved RFS both in ER+HER2+ and ER+HER2− groups, but did not improve OS in the ER+HER2+ group. Among 209 patients with HER2+ IBC, 134 received HER2 targeting therapies in neoadjuvant or adjuvant chemotherapy, and had a trend to improvement in RFS compared to chemotherapy alone (p = 0.082). The ER-HER2− group showed poorest outcome compared to other subgroups (P &lt; 0.001).

Conclusions: Sensitivity to NST differs depending on the ER and HER2 status in IBC pts. pCR rates based on these subgroups appear to be low. There is a need more effective treatments in the neoadjuvant and adjuvant therapies for all subgroups of IBC.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-05.