病理診断と画像所見に解離が見られた局所進行乳癌術前化学療法奏効例

Background Current American Joint Committee on Cancer (AJCC) breast cancer staging considers contralateral axillary metastasis (CAM) stage IV disease (M1). Retrospective studies suggest that women with CAM have improved overall survival (OS) compared to those with distant metastasis (M1) and/or comparable OS to locally advanced breast cancer (LABC). These studies support consideration of curative intent treatment; however, they contain heterogeneous cohorts with highly variable treatment strategies. We sought to evaluate treatment and outcomes in a well-defined CAM cohort treated with contemporary systemic and locoregional therapy. Methods We performed a retrospective multi-institution cohort study to compare OS of patients with CAM matched 1:3 on age +/- 5 years to LABC (defined as cN2-3 and/or pN2-3), and to non-CAM M1. CAM patients classified as type 1) de novo CAM, synchronous with the contralateral primary, 2) metachronous isolated CAM in the setting of prior surgical and/or radiation treatment to primary index cancer, 3) synchronous with, or 4) metachronous after an in-breast or axillary nodal recurrence of the primary index cancer. The M1 cohort included de novo and recurrent metastasis with varied sites and number of metastasis. OS was defined as time from CAM diagnosis to death or last follow-up for CAM patients; time from primary diagnosis to death or last follow-up for LABC; and time from metastatic diagnosis to death or last follow-up for M1. Unadjusted OS was estimated with the Kaplan-Meier method, and Cox proportional hazards models were used to estimate the association of group with OS after adjustment for covariates Results We identified 57 CAM and 155 LABC from 8 institutions (2016-2022), and 632 M1 from a single institution. The median age was similar between groups (CAM=59 years, LABC=58, M1=57, p=0.44), and there were no statistically significant differences in hormone receptor status (p=0.25). There were more Non-Hispanic Black patients in the M1 cohort compared to CAM or LABC (p< 0.001). The majority of CAM cases were delayed metachronous from the index cancer (type 2, 35.1%), or synchronous with a recurrence (type 3, 33.3%). Type 1 (de novo, 14%) and type 4 (delayed metachronous after breast cancer recurrence, 17.5%) were less frequent. Among CAM patients, 49.1% were hormone receptor positive (HR+)/HER2-negative (HER2-), 22.8% HR-/HER2-, 10.5% HR+/HER2+, and 5.3% HR-/HER2+. Comparing CAM versus LABC, invasive ductal carcinoma (IDC) was more commonly seen in CAM (82.5% vs 66.5%), as was grade 3 (45.6% vs 35.5%), and triple negative (22.8% vs 13.5%). Conversely, in LABC, treatment of the primary index cancer more frequently included chemotherapy (CAM=71.9%, LABC=92.3%), mastectomy (CAM=54.4%, LABC 74.2%), and adjuvant radiation (CAM=73.7%, LABC=90.3%). On multivariable analysis adjusting for age, race/ethnicity, and hormone receptor status, both CAM and M1 had inferior survival to LABC (Table 1), but with a 2.4-fold difference for CAM (95% CI 1.42-4.07, p=0.001) versus a 6.3-fold difference for M1 (95% CI 4.29-9.23, p=< 0.001). Discussion In this contemporary, multi-institution study, we demonstrated that CAM patients selected for presumed curative intent treatment experienced improved OS when compared to stage IV (M1) patients. Our data adds additional support for re-evaluating the current stage IV designation, in favor of N3, and consideration of curative intent treatment in this disease. Table. Adjusted* Overall Survival Comparing Patients with Breast Cancer Contralateral Axillary Metastasis (CAM) to those with Locally Advanced Breast Cancer (LABC) and Metastatic Disease (M1) *Adjusted for age, race/ethnicity, hormone receptors. Citation Format: Meghan R. Flanagan, Stephanie Downs-Canner, Samantha Thomas, Astrid Botty van de bruele, Margaret Lillie, Kristalyn Gallagher, Tammeza Gibson, James Jakub, Alexandra Verosky, Sarah Tevis, Malia Brennan, Francys Verdial, Jennifer Q. Zhang, Leisha Elmore, Jennifer Plichta, Laura Rosenberger. A Multi-Institutional Review of Contralateral Axillary Metastases: Time for Reclassification as Local-Regional Event? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-13.

Background: It is unknown whether molecular subtype is associated with axillary lymph node (ALN) status (ypN) after neoadjuvant therapy (NAT) in breast cancer patients who achieved breast pathological complete remission (pCR), especially for patients with different clinical stage. Our study aimed to investigate the association of clinical stage and molecular subtype with ALN status (ypN) after NAT in breast cancer patients. Patients and methods: Breast cancer patients receiving ≥ 4 cycles of NAT with complete clinicopathological data were retrospectively included between January 2009 to January 2020. Status of ypN according to breast pCR status was compared in cT1-2N0, cT1-2N1, and local advanced breast cancer (LABC) patients with different molecular subtype. Univariate and multivariate analyses were conducted to identify potential predictive factors for ypN status. Results: A total of 1999 patients were included. cT1-2N0, cT1-2N1, and LABC disease were found in 457 (22.86%), 884 (44.22%) and 658 (32.92%) patients, whose ypN+ rate was 24.5%, 60.3%, and 66.4%, respectively (P < 0.001). Compared with cT1-2N0 patients, ypN+ rate was significantly higher in cT1-2N1 (OR = 5.48, 95%CI = 3.77-7.97, P < 0.001) and LABC (OR = 10.90, 95%CI = 7.12-16.70, P < 0.001). Moreover, ypN+ rate varied across different molecular subtypes, which was 60.0% in Luminal A subtype, 61.4% in Luminal B (HER2-) subtype, 47.6% in Luminal B (HER2+) subtype, 42.2% in HER2-amplified subtype and 52.5% in TNBC (P < 0.001). Patients achieving breast pCR also had a significantly lower ypN+ rate than those without breast pCR (23.9% vs 62.5%, univariate P < 0.001; OR =0.14, 95%CI = 0.09-0.21, P < 0.001). Furthermore, in breast pCR patients, multivariate analyses showed that clinical stage and molecular subtype were substantially related to ypN+ rate: the ypN+ rate was significantly higher in cT1-2N1 (OR = 5.64, 95%CI = 2.31-13.76, P < 0.001) and LABC (OR = 9.80, 95%CI = 3.88-24.77, P < 0.001), compared with cT1-2N0 patients; while it was significantly lower in Luminal B HER2+ (OR =0.20, 95%CI = 0.05-0.82, P = 0.025) and HER2-amplified (OR = 0.19, 95%CI = 0.05-0.83, P = 0.026) subtype, compared with Luminal A subtype. In the cT1-2N0 subgroup, all patients with breast pCR with Luminal B HER2+ or HER2-amplified subtype achieved ALN pCR. Conclusion: Clinical stage and molecular subtype were significantly associated with ypN status in breast pCR patients after NAT. Patients with cT1-2N0 and HER2-positive patients who achieved breast pCR had low ypN+ rate, which possibly guides further clinical ALN management after NAT. Key words: Breast pathological complete remission; Neoadjuvant therapy; Molecular subtype; Clinical stage; Nodal residual burden. Table. Pathological node status stratified by clinical stage between patients with breast pCR and non-pCR.Response in breastpCRnon-pCRypN0 (N, %)ypN+ (N, %)ypN0 (N, %)ypN+ (N, %)Whole population331(76.1)104(23.9)586(37.5)978(62.5)cT1-2N088(93.6)6(6.4)257(70.8)106(29.2)cT1-2N1159(74.3)55(25.7)192(28.7)478(71.3)LABC84(66.1)43(33.9)137(25.8)394(74.2)Luminal A like9(69.2)4(30.8)37(36.3)65(63.7)cT1-2N06(85.7)1(14.3)19(73.1)7(26.9)cT1-2N13(50.0)3(50.0)12(27.9)31(72.1)LABC0(0.0)0(0.0)6(18.2)27(81.8)Luminal B like (HER2-)112(70.4)47(29.6)220(31.4)480(68.6)cT1-2N033(89.2)4(10.8)85(59.0)59(41.0)cT1-2N159(71.1)24(28.9)75(23.8)240(76.2)LABC20(51.3)19(48.7)60(24.9)181(75.1)Luminal B like (HER2+)89(83.2)18(16.8)140(42.4)190(57.6)cT1-2N019(100.0)0(0.0)70(83.3)14(16.7)cT1-2N146(83.6)9(16.4)43(30.5)98(69.5)LABC24(72.7)9(27.3)27(25.7)78(74.3)HER2 amplified66(82.5)14(17.5)97(48.0)105(52.0)cT1-2N014(100.0)0(0.0)42(82.4)9(17.6)cT1-2N125(78.1)7(21.9)32(42.1)44(57.9)LABC27(79.4)7(20.6)23(30.7)52(69.3)TNBC55(72.4)21(27.6)92(40.0)138(60.0)cT1-2N016(94.1)1(5.9)41(70.7)17(29.3)cT1-2N126(68.4)12(31.6)30(31.6)65(68.4)LABC13(61.9)8(38.1)21(27.3)56(72.7)Abbreviations: LABC, locally advanced breast cancer; HER2, human epidermal growth factor receptor 2; TNBC, triple negative breast cancer; pCR, breast pathological complete response. Citation Format: Jin Hong, Yiwei Tong, Ou Huang, Jiayi Wu, Li Zhu, Jianrong He, Weiguo Chen, Yafen Li, Xiaochun Fei, Xiaosong Chen, Kunwei Shen. Molecular subtype and clinical stage influenced axillary lymph node response in breast cancer patients with breast pathological complete remission after neoadjuvant therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-33.

Best management of locally advanced inoperable breast cancer

To the Editors: I read with interest Valero et al.'s review showing a lack of any increased cure rate over surgery from use of neoadjuvant combination therapy for locally advanced breast cancer, although a definite gain from breast conservation. Missing was any mention of hormone therapy [1] despite some of the best neoadjuvant results being from the use of Tamoxifen® in the elderly [2]. Interestingly, the highest complete remission rate in Valero et al.'s review (52%) was in a regimen including Tamoxifen® [3]. In addition, Bartlett et al. have reported that hormone therapy is superior to chemotherapy as adjuvant in estrogen receptor-positive tumors [4]. With new data from the study of radiotherapy demonstrating prostate tumor cell kill to be far higher when radiation treatment follows hormone therapy rather than when given concurrently or after therapy [5], there is a need for studies to investigate whether the same applies to hormone therapy when combined with chemotherapy in breast cancer. Further support for this comes from the latest overview of the effect of menstrual cycle timing and breast cancer surgery. The greatest gain from operating on premenopausal women occurs when the operation takes place during the progestergenic phase of the menstrual cycle, particularly in advanced node-positive patients and those with high levels of progesterone pre-op attributed to high survival [6]. With increasing recognition that trauma-induced cytokine release can be a factor in tumor acceleration [7], there is a case to consider hormones followed by chemotherapy plus radiation before any major surgical interference [1], most particularly in the rare subgroup of poor-risk tumors arising during pregnancy [8]. AUTHORS' RESPONSE: We appreciate the comments of Professor Oliver regarding our review. It has been recognized for decades that breast cancer is a systemic disease. Regional and distant micro- metastases occur early, and are part of the natural history of this illness. Adjuvant chemotherapy is an integral part of the curative management of patients with primary breast cancer, including locally advanced breast cancer (LABC). The benefit derived from this therapeutic approach is well documented, and persists beyond 10 years of follow-up [1, 2]. While we recognize the paucity of studies in direct support of this statement in patients with operable LABC, a few randomized trials have been completed and published [3, 4], and the world overview of randomized trials also demonstrated this benefit [1, 2]. Several randomized studies are under way to assess the relative efficacy of primary (or neoadjuvant) versus adjuvant chemotherapy in patients with early breast cancer, as well as operable LABC. For patients with inoperable LABC the window of opportunity to perform randomized trials with local therapy only as a control arm was lost many years ago. However, the results of phase II trials compare favorably with outcomes of historical control series. We agree that adjuvant hormonal therapy is also an integral part of optimal management of selected patients with LABC (those >50 years old, and with estrogen receptor-positive tumors). The world overview demonstrated an additive effect in women treated with both systemic modalities. Therefore, for this high-risk group of patients, combined hormone and chemotherapy for those who present with hormone-responsive breast cancer might be the treatment of choice. On the other hand, the role of neoadjuvant hormonal therapy alone remains to be defined. When we last reviewed this issue [5], only limited data were available, and the results did not appear superior to local treatments without systemic therapy. We (and others) are prospectively assessing the role of neoadjuvant tamoxifen in selected patients with LABC (those who are elderly and those patients unfit for chemotherapy). Professor Oliver's comments about other important areas in breast cancer research were beyond the scope of our review.

e12600 Background: Currently the treatment paradigm for locally advanced breast cancer (LABC) is multimodality therapy with neoadjuvant systematic treatment, surgery and postoperative radiation therapy (RT). However, with improving outcomes from systematic therapy, the survival rates remain unpromising, which leads to the investigation of the concept of preoperative RT in LABC due to the potential advantages including a possible tumor downstaging and better cosmetic outcomes. We evaluated the overall survival (OS) and breast cancer specific survival (BCSS) of preoperative versus postoperative RT in LABC patients. Methods: Patients diagnosed with non-inflammatory LABC (defined as T3 N1, T4 N0, any N2 or N3, and M0) who received RT before or after surgery between 2010 and 2015 were identified using the SEER database. OS and BCSS were analyzed using Kaplan-Meier method and multivariate Cox proportional hazards model. Results: Among 19249 patients with LABC, 140 (0.7%) received preoperative RT and 19109 (99.3%) received postoperative RT. Overall, 5-year survival and BCSS are 59% and 63% in the preoperative RT group while 77% and 80% in the postoperative RT group. In all patients, treatment with preoperative RT was significantly associated with poor OS (HR 1.82, 95%CI 1.25 to 2.45, P < 0.001) and BCSS (HR 2.00, 95%CI 1.46 to 2.73, P < 0.001) after adjustment for other clinically relevant factors. However, there were no significant difference in terms of both OS and BCSS in ER+ (OS: HR 1.44, 95%CI 0.91 to 2.27, P = 0.12; BCSS: HR 1.55, 95%CI 0.94 to 2.54, P = 0.08) and HER2+ patients (OS: HR 1.33, 95%CI 0.55 to 3.22, P = 0.53; BCSS: HR 1.64, 95%CI 0.67 to 3.97, P = 0.28). Conclusions: Overall, preoperative RT in LABC may reduce overall survival and breast cancer specific survival. However, OS and BCSS were independent of radiation sequence for ER+ and HER2+ patients. This finding warrants further exploration of potential mechanisms of the disparity and the definitive role of preoperative RT in the multimodality therapy of LABC patients.

Preoperative systemic therapy including neoadjuvant chemotherapy (NCT) is standard treatment in locally advanced breast cancer (LABC), the aim of which is to enable a radical surgery and to reduce the risk of local and distant recurrence. It has been established that NCT in LABC may effectively induce apoptosis. The study objective was to assess the role of a proapoptotic second mitochondria-derived activator of apoptosis (SMAC) in LABC. The study group comprised 56 patients with advanced non-metastatic breast cancer (stage IIB -node positive and III), who received NCT followed by surgery and adjuvant treatment. Expression of SMAC protein was analysed using the immunohistochemistry technique in core biopsies sampled from the patients' breasts before NCT and in surgical specimens collected after completion of NCT. Expression of SMAC was significantly higher in the breast cancer specimens after NCT (p < 0.01). High expression of SMAC in the core biopsy before NCT correlated with a pathological complete remission (pCR, p < 0.01). The patients with a high expression of SMAC in the surgical specimens after NCT had longer DFS. Our study proves a potential role of SMAC expression in LABC as a novel favourable prognostic factor in LABC for pCR and disease-free survival (DFS).

Background: Integration of neoadjuvant chemotherapy (NCT) in early 70s resulted that many LABC tumors become resectable but with total mastectomy especially those with partial response, oncoplastic techniques give better oncological outcome with better cosmetic results. Objective: We evaluate the oncological safety of oncoplastic breast surgery (OS) in LABC showing partial response to NCT. Methods: We prospectively analyzed the data of 32 out of 58 patients with LABC who showed partial response to NCT and could have conservative surgery with advanced oncoplastic techniques rather than total mastectomy. Results: Out of 58 patients with LABC, received neoadjuvant chemotherapy, complete response was observed in 8 patients (13%), partial response reported in 32 (55.1%) cases, 12 patients (20%) had stable disease and 6 patients (10%) showed progressive disease. Data of 32 cases were studied (mean age 44.84 ± 9.10 years; range 26 - 59 years). Inferior pedicle was performed in 9 cases, mini LD flap in 3 patients, 5 had Grissotti technique, 6 with superomedial pedicle, 4 had V mammoplasty and 3 with J mammoplasty and 2 had vertical mammoplasty. Margins were positive in 5 cases (15.6%) with mean margin width 9.63 ± 5.72 (range 0 - 22 mm), and the local recurrence was reported in 2 cases (6.2%). Complications were reported in 3 cases (9.3%). The follow up was 1.67 ± 1.03 (range 0 - 3.3 years). Conclusions: Integration of neoadjuvant chemotherapy together with advanced oncoplastic techniques opens a new way for management of LABC especially those showing partial response with avoidance of total mastectomy, and comparable oncological safety in addition to better aesthetic and psychological outcome.

Locally advanced breast cancer (LABC) is one of the subgroups of invasive breast cancer. The treatment of LABC is neoadjuvant chemotherapy (NAC) before surgery, which is different from the others. The study aimed to analyze and compare the characteristics of conventional ultrasound, contrast-enhanced ultrasonography (CEUS) and strain elastography (SE) in LABC patients who have different treatment outcomes, and to provide help for LABC in the imaging diagnosis and clinic treatment. From May 2018 to April 2019, 36 patients (40 lesions) of LABC were enrolled, which diagnosed by puncture biopsy. According to the clinical evaluation, these patients were recommended to undergo pre-operative NAC followed by surgery. All patients underwent conventional ultrasound, CEUS and SE before puncture. According to postoperative pathological grading and follow-up, the patients were divided into effective and ineffective groups. We summarized and compared the features of conventional ultrasound, CEUS and SE of patients in two groups. The correlation between the imaging characteristics and the postoperative pathological grading was also analyzed. Conventional ultrasonic features of LABC: the most lesions of LABC were mass type (32/40, 80.0%), and all lesions were irregular. Most of lesions showed unclear boundaries (39/40, 97.5%), heterogeneous echoes (38/40, 95.0%), and internal calcifications (24/40, 60.0%). Most of lesions had hyperechoic halos (31/40, 77.5%), aspect ratio less than or equal to 1 (34/40, 85.0%), and blood flow grading was III (36/40, 90.0%). CEUS features of LABC: compared with the surrounding normal tissues, all the lesions (40/40,100.0%) were highly enhanced. Most of lesions (35/40, 87.5%) were uneven enhanced. The main enhancement mode was "fast in and slow out" (39/40, 97.5%). There were totally 25 lesions which had "solar sign" (25/40, 62.5%). SE features of LABC: the average visual elastography score of the lesions was 4.28±0.67, the maximum strain rate (E1) of the lesions averaged 4.88±0.54, and the overall strain rate of the lesion averaged 4.14±0.72. There was no significant difference between effective and ineffective groups in the characteristics of conventional ultrasound, CEUS and SE. There was a correlation between the appearance of "solar sign" in CEUS and postoperative pathological grading, and the contingency coefficient was 0.564 (P<0.05). The pathological grading of patients without solar sign was higher. The other characteristics of conventional ultrasound, CEUS and SE in LABC patients had no correlation with postoperative pathological grading. In LABC, the conventional ultrasound usually shows irregular shape and unclear boundaries. The aspect ratio is less than or equal to 1. CEUS showed uneven enhancement of "fast in and slow out", and "solar sign" was often seen. Elastography showed that the texture of the lesion was significantly stiffer than the surrounding normal tissue. Ultrasound imaging before NAC had no relationship with pathological complete response or not. However, "solar sign" in CEUS was an important feature and had correlation with postoperative pathological grading.

The utility of neoadjuvant chemotherapy is expanding in the treatment of breast cancer. Although individual trials have shown comparable survival between patients receiving neoadjuvant and adjuvant chemotherapy, large-scale data analyses for outcomes in patients with locally advanced breast cancer (LABC) are lacking. We conducted an individual-level statistical analysis using patients from six randomized controlled trials (RCTs) investigating survival outcomes with neoadjuvant versus adjuvant chemotherapy in breast cancer by abstracting and analyzing only the patients with LABC. Individual patient data for 779 patients with LABC were collected from six RCTs. Overall and disease-free survival rates were compared between patients receiving neoadjuvant vs. adjuvant chemotherapy with the Cox hazard model and log-rank statistics. Since chemotoxicity causing delays to surgical care is a potential drawback of neoadjuvant chemotherapy, local cohort data were then employed to assess the actual incidence of this, along with the causes behind any delays to surgery in patients receiving neoadjuvant chemotherapy. A time interval from neoadjuvant chemotherapy to surgery of >8 weeks was investigated in a local cohort of 563 patients, representing all locally treated patients receiving neoadjuvant chemotherapy between 2006 and 2019. The statistical analysis demonstrated no overall or disease-free survival differences in LABC patients receiving neoadjuvant vs. adjuvant chemotherapy (p = 0.96 and 0.74, respectively). Within our cohort, 31 (5.5%) patients treated with neoadjuvant chemotherapy experienced a delay of >8 weeks to surgery, with only 13 (2.3%) attributed to chemotherapy-related complications. Our study provides further support for the paradigm shift towards delivering chemotherapy for breast cancer patients in the neoadjuvant setting.

551 Background: Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). Liquid biopsy, including circulating tumor cells (CTCs) and cell free DNA (cfDNA) represent an important paradigm shift in precision medicine. The aim of this study was to estimate the value of CTCs and cfDNA in efficacy prediction of the response to NCT in patients with LABC. Methods: Patients with LABC received EC4-T4 regimen NCT. CTCs and cfDNA obtained at time of biopsy, after first course of NCT and after the last course of NCT. All patients were divided into two groups according to pathological reactivity. A novel SE-iFISH strategy, improved for detection of CTCs, was applied. CTCs(CD45-/CD31-) with different cytogenetic abnormality of aneuploid chromosome 8 and small cell size CTCs (≤5 mm of WBCs) were analyzed separately in LABC patients subjected to NCT for the first time. Plasma DNA biomarkers ALU 111 and ALU 260 elements were evaluated using qRT-PCR. DNA integrity was calculated relative to the breast cancer cell line MCF-7. Clinical significance of diverse subtypes of CTCs and cfDNA was systematically investigated. Results: A total of 45 patients was enrolled in this study. According to the therapy response, 6/45 patients had high response (High-R) and 39/45 patients had low response (Low-R). There were no significant differences in CTC number and small cell size CTC number between High-R and Low-R groups in all three detections. However, the CTC number kept stable in the High-R group, but increased continually during NCT in Low-R group. In 45 patients, the percentage of CTCs with trisomy 8, which were related to cancer metastasis, incresed in the Low-R group at the third dectection. The concentration of cfDNA in all three detections did not indicate outcome of NCT. However, concentration of ALU 111 increased in Low-R patients during NCT. In High-R patients, no significant increase was observed. A CTC and cfDNA panel were constructed to discriminate High-R patients from Low-R patients. The areas under the receiver-operating characteristic (ROC) curves of the pannel for the three times were 0.803, 0.859 and 0.667, respectively. DNA integrity index(CFDI) was significantly higher in High-R group than Low-R after first course of NCT. The areas under the ROC curves of the CFDI for the three times were 0.675, 0.863 and 0.697, respectively. Conclusions: The trend of cfDNA concentration changed resembled to the number of CTCs, small cell size CTCs and triploid CTCs during NCT, and could predict tumor response to ongoing treatment.

Clinical Effects of Shenqi Fuzheng Injection in the Neoadjuvant Chemotherapy for Local Advanced Breast Cancer and the Effects on T-lymphocyte Subsets

e11614 Background: Preoperative chemotherapy (PCT) is the standard of care for locally advanced breast cancer (LABC). As part of a multicentre provincial initiative we undertook a review of practice patterns and outcomes for women with LABC at our institution. Methods: We reviewed electronic and paper records for M0 pts receiving PCT for LABC between 1995–2007 at our institution, collecting demographic, disease and treatment-related, and outcome variables. Results: Sixty pts with LABC who received PCT were included in this review. Median age was 54y (31–80), 38% premenopausal. Median BMI was 28kg/m2, 78% were overweight or obese. Stage distribution: 10% IIB, 11% IIIA, 77% IIIB and 2% IIIC, of which 45% had inflammatory breast cancer (IBC). At biopsy 90% were invasive ductal carcinoma, 36% were ER and PR(-) and 25% were her2(+). Median time from surgical consultation to PCT was 22d (6–126). PCT was anthracycline-based alone in 85% of pts, 8% received a taxane, 3% also received preop endocrine therapy (ET), no pts received trastuzumab (T) preop. Pts received a median of 6 (3–8) cycles of PCT. Local therapy: mastectomy (M) in 82% of pts and partial M in 11%. Axillary surgery was done in only 92% of pts (axillary node dissection 90%, sentinel node biopsy 1pt) and 7% had no definitive breast or axillary surgery due to local progression (3) or refusal (1). All pts received radiotherapy. Postop systemic therapy: CT in 5% of pts, ET in 65% and T in 10% of pts. Clinical complete response (CR) rate was 28%. At definitive surgery 10% of pts had no residual disease in breast or axilla and 3 pts had only DCIS present, for a pathologic (p)CR rate of 15% using MDACC criteria. Median follow-up was 24mo (1–238). Median 5y DFS was not reached for the entire population and those with a pCR vs. 26mo for pts with IBC; corresponding 5y DFS rates were 58%, 78%, and 41% respectively. Median 5y OS was for the entire population was 52mo vs. 48mo for pts with a pCR and 47mo in the IBC group; corresponding 5y OS rates were 62%, 78% and 44% respectively. Conclusions: Management of LABC in our cohort is fairly uniform and consistent with current guidelines. Local outcomes of LABC managed with PCT are in keeping with the published literature and arguably better since almost half of our cohort is represented by IBC which carries a worse prognosis. No significant financial relationships to disclose.

11511 Background: At UI a unique, highly intensive myeloablative regimen of cisplatin, etoposide, thiotepa and cyclophosphamide (PET-CY) was utilized for patients (pts) with high risk breast cancer. Methods: Records of 97 consecutive, clinical trial pts with LABC and IBC were reviewed. Pts were rigorously screened to exclude systemic disease. Univariate analyses were performed for overall survival (OS) and disease-free survival (DFS). Treatment-related mortality (TRM), frequencies of life-threatening toxicities and second malignancies were also reviewed. Results: Median follow-up among 44 current survivors was 9.6 years (3.5 - 15.2). For all pts the median tumor size at surgery was 3.5 cm and the median number of involved lymph nodes was 11. Neoadjuvant chemotherapy had been given in 70% of pts with IBC and 13% pts with LABC. OS and DFS are reported in the table. Tumor sizes, E-E grade, surgery type, date from diagnosis to transplant, and neoadjuvant treatment did not influence OS or DFS. In patients with LABC, ER positive patients had statistically significant improved OS (HR for death 0.45, p = 0.03). TRM at 100 days was 11%. 16% of patients had life threatening complications. Stomatitis was frequent and severe: 6 patients required intubation for this. Second cancers developed in 8 patients. Conclusions: This analysis provides long-term follow-up on patients treated with PET-CY myeloablative regimen with ASCT for high risk breast cancer. Treatment related morbidity and mortality were high. Fewer second malignancies were seen than have been reported in other series. These data provide an estimate of long-term outcome for patients with high-risk breast cancer, screened for participation in a clinical trial to exclude systemic disease and treated with a highly intensive, multi-agent chemo-ablative regimen. Survival rate of overall survival and disease-free survival Survival Rate (95% CI) Inflammatory Breast cancer Locally Advanced Breast Cancer Overall 100 days 0.87 (0.69, 0.95) 0.89 (0.79, 0.95) Survival 5 years 0.54 (0.36, 0.70) 0.65 (0.52, 0.75) 10 years 0.35 (0.17, 0.55) 0.47 (0.33, 0.59) Disease-free survival 100 days 1 0.97 (0.87, 0.99) 5 years 0.59 (0.39, 0.75) 0.67 (0.54, 0.78) 10 years 0.53 (0.31, 0.71) 0.49 (0.35, 0.67) No significant financial relationships to disclose.

Introduction: Breast cancer (BC) is a serious health concern. Neoadjuvant chemotherapy (NAC) is a crucial therapy for managing BC, but further research is needed to identify biomarkers that can help to predict the efficacy of this therapy. The presence and functional activity of tumor-associated neutrophils (TANs) are capable of serving as predictive biomarkers for therapeutic outcomes. Elevated neutrophil-to-lymphocyte ratio (NLR) is linked to high tumor stage and low histological grade, indicating a more aggressive disease profile. This study analyzed the relationship between TAN expression and NLR with clinical response to NAC in locally advanced BC (LABC). Methods: This was a cohort study of 41 patients with BC. TAN expression was examined using immunohistochemistry, NLR was obtained from routine blood tests, and chemotherapy response was assessed using the RECIST method. The relationship between TAN expression and NLR with chemotherapy response in LABC was tested using chi-square tests. Results: High and low TAN expression was observed in 80.5% and 19.5% of patients, respectively. For NLR before chemotherapy, 48.8% and 51.2% of patients exhibited a high and low NLR, respectively; after chemotherapy, 51.2% and 48.8% of patients exhibited a high and low NLR, respectively. Moreover, 90.2% patients responded to NAC. A significant relationship was observed between TAN expression and chemotherapy response in BC, with a moderately strong negative correlation. Conclusion: TAN expression is an important potential predictor of chemotherapy response in LABC. By identifying biomarkers like TAN, clinicians may be better able to customize treatment plans and enhance outcomes for patients with LABC.

608 Background: For the treatment of LABC using a regimen with the highest likelihood of shrinking the tumor should improve the outcome. Paclitaxel was the first taxane to show activity in breast cancer. The advent of endocrine therapy in the neoadjuvant setting allows downstaging of tumors with less morbidity. The aromatase inhibitors are now the treatment of choice in neoadjuvant setting for elderly patients with estrogen receptor-positive breast cancer. Methods: This prospective, randomized, comparative study assessed the effect of three cycles of neoadjuvant chemotherapy vs. three months of neoadjuvant hormonal therapy in terms of loss of clinical and pathological primary tumor size. Inclusion criteria required postmenopausal patients with non-metastatic, ER and/or PR positive LABC with no co-morbidity. Forty eligible patients were randomly assigned into 2 groups of 20 patients each: Group A treated with 3 cycles of 3 weekly injections of paclitaxel (175 mg/m2) and carboplatin (AUC 6) assessed after each cycle; group B received oral Letrozole 2.5mg once daily for 3 months assessed every 4 weeks. Surgery was done and primary specimen was pathologically examined. Results: Clinically mean loss in primary residual tumor compared to volume at presentation in group A vs. group B at 1st review was 45% vs. 35% (p: 0.536), 63% vs. 57% at second (p: 0.176), and 71% vs. 74% at third review (p: 0.062).Clinical complete response (WHO criteria) and stable disease each were seen in 14% in either group of patients (p: 0.632), partial response in 65% group A and in 72% group B (p: 0.117); no progressive disease was seen in either. All patients underwent surgery. The mean pathological primary cell kill in group A vs. group B was 81% vs.78 %(p:0.918). Resected nodes were pathologically positive for tumor in 47% group A and 60% group B patients (p: 0.269). Conclusions: Neoadjuvant hormonal therapy using oral Letrozole in receptor positive LABC in post menopausal women is as effective as three weekly paclitaxel and carboplatin in downstaging the tumor. No significant financial relationships to disclose.