McGuire, KP

Abstract Background:Neoadjuvant chemotherapy (NCT) is used frequently to downstage locally advanced tumors and facilitate breast conservation. However, we have previously reported that achievement of radiographic complete response (rCR) or pathologic complete response (pCR) does not impact choice of surgery for many patients. This secondary analysis reports treatment outcomes across 9 NCI comprehensive cancer centers in women receiving both NCT and breast MR imaging to assess whether treatment outcomes among women receiving NCT differs according to choice of locoregional treatment. Methods:1077 women from 9 institutions were retrospectively identified as having undergone NCT with MR imaging obtained both before and after systemic treatment. Systemic treatment regimen was not prespecified, but receipt of at least 80% of all planned cycles was required prior to final MR imaging. We performed a univariate analysis as well as a multivariable Cox proportional hazard regression to identify covariates associated with overall survival (OS), disease-free survival (DFS) and time to recurrence (TTR). rCR was defined as no residual enhancement on post-treatment breast MRI. Results:1077 patients diagnosed and treated with NCT for stage I-III invasive breast cancer from January 1, 2002 to June 16, 2014 were analyzed for all endpoints. Median follow-up was 4.2 years, (range 0.1 to 13 years). Median age of the cohort was 50 years, (range 19-87 years). 473 (43.9%) had ER(+) and/or PR(+)/HER2(-) disease, 348 (32.3%) had HER2(+) disease, and 256 (23.8%) had ER(-)/PR(-)/HER2(-) (triple negative) disease. Mastectomy or breast conserving therapy (BCT) was recorded as the definitive surgery in 675 (62.7%) and 402 (37.3%) of patients, respectively. Radiation receipt was confirmed in 84.1% of BCT and 68.3% of mastectomy patients. Overall there were 134 recurrences, 168 disease events and 89 deaths. Among patients with pCR, there were 7/161 (7.2%) recurrences in those undergoing mastectomy and 6/143 (5.1%) in those undergoing lumpectomy (p=0.81). Among patients who achieved an rCR, there were recurrences in 5% of those undergoing mastectomy and 2.9% in those undergoing lumpectomy (p=0.53). In multivariable analysis of the entire cohort, only clinical stage, ER status and pCR remained independently associated with DFS. Notably, subset analysis showed that lumpectomy was independently associated with improved TTR (HR 0.40; 95% CI 0.17-0.97) in the triple negative group only, but this did not translate into improved DFS with lumpectomy in this group. Radiographic CR as determined by breast MRI accurately predicted presence or absence of pCR in 74% of cases, but was not independently associated with DFS, OS or TTP. Conclusions:Among a contemporary cohort of women receiving neoadjuvant systemic therapy and breast MR imaging at 9 NCI designated cancer centers, type of surgery did not impact DFS, OS or TTP. The only exception was found in the triple negative group in which the lumpectomy group had a more favorable TTP compared to the mastectomy group. These findings provide additional evidence that in women who are appropriate candidates for lumpectomy after NCT, BCT does not compromise long-term cancer outcomes. Citation Format: De Los Santos J, Hyslop T, Alvarado M, Forero A, Golshan M, Hieken T, Horton J, Hudis C, McGuire K, Meric-Bernstam F, Nanda R, Zagar T, Hwang S. Treatment outcomes in patients with invasive breast cancer treated with neoadjuvant systemic therapy and breast MR imaging: Results of a secondary analysis of TBCRC 017. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S3-06.

Abstract Background: Retrospective studies suggest that primary breast surgery is associated with improved overall survival (OS) in Stage IV breast cancer. TBCRC 013 is a multi-center prospective registry study evaluating the role of surgery for the primary tumor in Stage IV disease. Methods: From 7/09 - 4/12, 128 eligible pts from 14 sites were enrolled in two cohorts (A: Stage IV with intact primary tumor (n = 112); B: metastases (mets) within 3 months of primary surgery (n = 16)). Baseline patient and tumor characteristics, and surgery of the primary were correlated with 2yr overall survival (OS) using log rank, Kaplan Meier and Cox regression for all patients. Comparisons were also made between cohorts A and B and within cohort A stratified by response to systemic therapy. Responders included those with any response (partial,complete) or stable disease at distant sites. Results: Median pt age was 52yrs(21-79) and median primary tumor size 3.2cm(0.7-15). Phenotypes were ER+ 106 (83%), HER2neg 91(71%), and triple neg 10(8%). 60(47%) had bone-only mets. The only significant baseline difference between cohorts A and B was the presence of palpable nodes (A:62% vs B:0%, p<0.001). There were no differences in age, tumor size, ECOG scores, ER or HER2 status, number or sites of mets between cohorts A and B. At a median follow-up of 25 mo (95%CI, 23-31), 2yr OS for all pts is 86% (80-92) and is superior in cohort B as compared to A, (100% vs 84%, p = 0.03). On multivariate analysis (MVA) including all pts, only surgery, ER and HER2 positivity were associated with improved OS (table). Among 112 pts with an intact primary (Arm A), 17(15%) were non-responsive (NR) to systemic therapy, 3(18%) of whom required palliative surgery at a median time of 10.4mos. 2yr OS among NR was 33% (15-69) as compared to 94% (88-99) in Arm A responders (R) (p<0.001). ER positivity was the only baseline difference between NR (65%) and R (88%) within Arm A (p = 0.02). Among 94(85%) Arm A responders, 39(41%) had elective surgery (median 8.4 mos, 95%CI:6.9-10.3) and only 1 of the remaining 47(2%) required palliation. When limited to Arm A responders, elective surgery was not associated with improved 2yr OS (surgery vs not: 94% vs 92%, p = 0.5). Median time to progression following elective surgery was 12 mos (95%CI,8-19mos). When cohort B (n = 16) and cohort A surgery groups (n = 39) are combined, surgery of the primary tumor is associated with improved 2yr OS (96% vs 74%, p = 0.002). Conclusions: In this prospective registry study, patients diagnosed with mets within 3 months of primary breast surgery have an improved 2yr OS. When all pts having surgery (A + B) are examined, surgery is associated with improved OS on MVA, but when limited to Arm A responders, elective surgery does not improve OS. Given that the number of Arm A responders is small, results from the prospective randomized trial will be needed to address this question. These data also demonstrate that the need for surgical palliation of the primary tumor is uncommon in the modern era. Multivariate Analysis for OSN = 128HR Death (95%CI)pvalueSurgery0.28 (0.10-0.74)0.01ER positivity0.28 (0.10-0.72)0.01HER2 positivity0.21 (0.06-0.74)0.01MVA included: age, tumor size, ECOG, ER, PR, HER2, met sites, and surgery Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-09.