Abstract P4-14-01: Changes in treatment and improved survival of inflammatory breast cancer (IBC/T4d) and T4a-c lesions: 1990-2014
Authors: Malmgren JA , Atwood MK , Kaplan HG 
Published: February 2018

Background: T4 breast cancer (BC) is a tumor of any size with direct extension to the chest wall and/or to the skin. Tumor stage T4a-d including IBC (T4d) are aggressive cancers, often presenting with distant metastases or progressing quickly to metastatic breast cancer (MBC).

Methods: We conducted a retrospective cohort analysis of invasive BC cases with T4 tumor stage from a prospectively collected institutional BC registry, years 1990-2014 [total N = 10,414, all T4 = 320 (T4a = 20, T4b = 130, T4c = 15, T4d (IBC) = 155)]. Presentation at diagnosis by hormone receptor (HR) and her2-neu (HER2) status, treatment, follow up for distant metastases and vital status were reviewed. Change in treatment over time was compared using Pearson chi square tests. Disease specific survival (DSS) was estimated using Kaplan Meier plots. Cox proportional hazards modeling was used to obtain T4 adjusted hazard ratio (HzR) among MBC (de novo and distant recurrence) patients (n=1158).

Results: T4 tumor stage cases were 3% of the total cohort but 10% of relapsed MBC and 28% of de novo MBC cases (p&lt;.001).T4 cases were significantly more often HR negative (35%) (p &lt; .001). After 1999 when HER2 results were available, T4 was significantly less often HR+/her2- (52%), and significantly more often HR+ or -/HER2+ (28%) and triple negative (20%) (TN = HR-/HER2-) than the rest of the cohort (p &lt; .001). No change over time in number or percent treated with surgery, radiation, chemotherapy, neoadjuvant therapy, hormone therapy or combinations was observed. Chemotherapy changed significantly over time with the introduction of trastuzumab treatment for HER2+ disease in 1999 and increasing from 60% for HER2+ disease in 1999-2004 to 100% in 2005-14 (p &lt; .001). The shift to combination doxorubicin/cytoxan/taxane from 13% in 1990-98 to 43% in 1999-2014 was also significant (p &lt; .001). T4 5 year DSS improved from 45% in 1990-1998 to 68% in 1999-2014 after the introduction of her2-neu testing and new treatments (p = .001). Survival improvement over time was significantly greater among T4 cases than T1-T3 cases [ T1 = 2%, T2 = 5%, T3 = 5%, T4 = 23% (p &lt; .001)]. In a Cox proportional hazards model of MBC patients, outcome = BC mortality, adjusted for race, diagnosis year, age, HR status, number and type of metastatic sites, T4 status was associated with an 18% decreased chance of mortality [HR=.82, 95% confidence interval = .68, .988, p =.048].

Cox proportional hazards model (n=1158)factorHzR (95% CI)p valueHR-1.64 (1.41, 1.91)&lt;.001age 70+ years1.97 (1.65, 2.34)&lt;.001recurrent MBC vs de novo MBC1.91 (1.61, 2.26)&lt;.001&gt;= 2 metastatic sites1.38 (1.19, 1.60)&lt;.001visceral dominant mets site1.23 (1.05, 1.44).012T4 primary tumor.82 (.68, .998).048

Conclusions: T4 BC is disproportionately triple negative, HER2+, diagnosed as stage IV MBC or distant recurrent MBC compared to T1-T3 stage category disease. T4 disease, including IBC, has had the largest improvement in disease free survival over time of all BC subtypes and is a factor associated with better MBC survival. Despite the small overall number of patients presenting with T4 tumor stage disease, the dramatic reduction in T4 mortality over time has a large impact on survival improvement.

Citation Format: Malmgren JA, Atwood MK, Kaplan HG. Changes in treatment and improved survival of inflammatory breast cancer (IBC/T4d) and T4a-c lesions: 1990-2014 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-14-01.