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Abstract PO3-07-06: Correlation between residual microcalcification and in-breast pathologic response in relation to MRI response and the subtypes after neoadjuvant chemotherapy

Abstract Background The significance of residual microcalcifications after neoadjuvant chemotherapy (NAC) in determining the extent of surgical intervention in breast cancer remains unclear. This study aimed to assess whether residual microcalcifications after NAC correlate with the residual disease in patients with breast cancer stratified by subtypes, particularly in excellent radiologic responders. Methods We conducted a retrospective study of patients with breast cancer who underwent NAC followed by curative surgery between January 2007 and December 2022. We evaluated the presence of suspicious microcalcifications on pre-NAC mammography and residual microcalcifications on post-NAC mammography. In the patients who had residual microcalcifications on post-NAC mammography, the rates of breast pathologic complete response (pCR), defined as the absence of invasive cancer (ypT0/is) or complete breast pCR defined as the absence of invasive cancer and in-situ cancer in the breast (ypT0), was assessed according to the MRI response and subtypes. We defined complete MRI response as the resolution of suspicious enhancement in the breast and axilla after NAC. Results Of the 1078 patients, 554 (51.4%) had suspicious microcalcifications at baseline, of which 518 (93.5%) had residual microcalcifications after NAC. Among the 518 patients with residual microcalcifications, 93 (18.0%) achieved a complete MRI response. We observed a difference in breast pCR rates depending on MRI response and hormone-receptor (HR) status. In the patients without complete MRI response, about one-third of patients (139 of 425 [32.7%]) achieved a breast pCR, irrespective of HR status (19.3% [47 of 244] in HR-positive breast cancer and 50.8% [92 of 181] in HR- negative breast cancer). Of the 93 patients who achieved a complete MRI response, the breast pCR rates were 64.3% (27 of 42) in HR-positive breast cancer and 96.1% (49 of 51) in HR-negative breast cancer, respectively. Moreover, the breast complete pCR rate was 54.8% (23 of 51) in HR-positive breast cancer and 88.2% (45 of 51) in HR-negative breast cancer, including 87.2% (34 of 39) in HR-HER2+ breast cancer and 91.7% (11 of 12) in triple-negative breast cancer. Conclusion Our results suggest that the clinical relevance of the residual microcalcifications differs according to the breast cancer subtypes. For patients with HR-positive breast cancer, removal of the residual microcalcifications should be considered to ensure complete cancer removal, regardless of MRI response. In contrast, de-escalating surgery may be considered in patients with HR-negative breast cancer who achieve complete MRI response after NAC. Citation Format: Soong June Bae, Seung Ho Baek, Seung Eun Lee, Min Ji Kim, Sohyun Moon, Junghyun Kim, Yoonwon Kook, Joon Jeong, Sung Gwe Ahn. Correlation between residual microcalcification and in-breast pathologic response in relation to MRI response and the subtypes after neoadjuvant chemotherapy [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 PO3-07-06.

Abstract PO5-02-10: Favorable effect of HER2-low expression on prognosis for breast cancers after neoadjuvant chemotherapy

Abstract [Background] The clinicopathological characteristics, pathological complete response and survival outcomes of HER2-low, HER2-zero and HER2-positive breast cancers are yet to be elucidated in Chinese patients especially those administered neoadjuvant chemotherapy. [Methods] We retrospectively identified 259 patients with different HER2 statuses (zero, low and positive) who underwent surgery as planned after neoadjuvant chemotherapy from a prospectively maintained institutional cohort database in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between 2014 and 2019. Overall survival (OS) denoted the time from surgery to death, irrespective of cause. Locoregional relapse-free survival (LRFS) was estimated from surgery to first occurrence of locoregional, ipsilateral relapse, or death, irrespective of cause. We defined pathologic complete response (pCR) as ypT0 ypN0 (absence of cancer in the breast and axillary nodes). The definition of ypT0/is ypN0 (absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ) was evaluated as an additional endpoint. [Results] A total of 89 (34.36%), 66 (25.48%) and 104 (40.16%) HER2-low, HER2-zero and HER2-positive breast cancers were enrolled in this analysis, respectively. The median follow-up interval was 5.74 years. Hormone receptor(HR) expression was numerically more common in HER2-low breast cancers than the other two subgroups (83.15% in HER2-low vs 72.73% in HER2-zero vs 77.88% in HER2-positive, P >0.05). The level of Ki-67 index was significantly lower in the HER2-low tumors than that of HER2-zero tumors (P=0.023). HER2-positive tumors had the highest proportion of histological grade III (P=0.005). The HER2-low breast cancers showed significantly better OS (P=0.0056) and LRFS (P=0.002) than HER2-zero counterparts. Subgroup analysis revealed the similar benefit in LRFS (P=0.018) rather than OS (P=0.055) for patients with HR positive/HER2-negative tumors. When the HER2-positive tumors was combined together for comparison, the OS (P=0.016) and LRFS (P=0.0062) also significantly differed among patients with HER2-low, HER2-zero, and HER2-positive tumors. Additionally, the HR negative patients had analogous OS outcome to the entire population according to different HER2 status (P=0.041). Multivariable Cox-regression analysis and external validation in the TCGA database as well as Kaplan-Meier plotter database supported that HER2-low tumors and HER2-positive tumors treated with HER2-directed therapy may have similar survival outcomes, while HER2-zero peers may have the worst outcome compared with the above two groups. There were no remarkable differences in pCR rates between HER2-low and HER2-zero tumors after neoadjuvant chemotherapy (ypT0ypN0 and ypT0/isypN0, P=0.452 and P=0.777, respectively). HER2-positive tumors had a significantly higher pCR rate, especially compared to HER2-low tumors in the entire population (both P< 0.001) as well as in the HR positive subgroup (both P< 0.0001). The pCR status affected survival outcomes for breast cancers with different HER2 status. As for those without pCR, the HER2-low subgroup showed a remarkably better performance compared with HER2-zero patients in terms of OS (P=0.018) and LRFS (P=0.005), while little difference was found for patients who achieved pCR. [Conclusion] Our study demonstrated that HER2-low breast cancer may be a different entity from HER2-zero or HER2-positive tumors, which provide illuminating evidence in view of patients receiving neoadjuvant treatment. Citation Format: Yingying Zhao, Wenjin Yin, Xinru Chen, Jingsong Lu. Favorable effect of HER2-low expression on prognosis for breast cancers after neoadjuvant chemotherapy [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 PO5-02-10.

Abstract PO2-28-07: Artificial Intelligence-based Computer-aided Diagnosis for Mammography: Predicting Occult Invasive Cancer in Women with Biopsy-proven Ductal Carcinoma in Situ

Abstract Background: Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer confined within the basement membrane. Due to the increase in breast cancer screening, DCIS is increasingly being diagnosed on biopsy. Active surveillance is a novel and evolving treatment strategy for DCIS to reduce overtreatment. Currently ongoing clinical trials of active surveillance include only mammographic findings in their eligibility criteria, however mammography has limited ability to detect occult invasive cancer. The objective of this study was to investigate whether an artificial intelligence-based computer-aided diagnosis (AI-CAD) application for mammography can improve the prediction of occult invasive cancer in women with percutaneous needle biopsy-proven DCIS. Methods: A retrospective search of our database identified consecutive women with percutaneous needle biopsy-proven DCIS who underwent surgery at Seoul National University Hospital (Seoul, Korea) between June 2019 and May 2021. Two board-certified breast radiologists reviewed preoperative mammographic findings of the primary tumor in consensus according to the Breast Imaging Reporting and Data System. Using a commercially available AI-CAD (Lunit INSIGHT for Mammography, Lunit Inc.), quantitative abnormality scores of 0 to 100% of the ipsilateral breast were obtained. Data were collected on age at diagnosis, symptoms, biopsy methods, DCIS grade on biopsy, and presence or absence of invasive cancer and axillary lymph node metastases on surgical pathology. Multivariable logistic regression models were used to evaluate factors associated with prediction of occult invasive cancer. Results: Of 692 biopsy-proven DCIS in 692 women (mean age, 53 years ± 11 [standard deviation]), 298 (43%) presented as calcifications only, 160 (23%) as mass or asymmetry, and 111 (16%) as masses with calcifications. The other 123 (18%) cancers were not demonstrable on mammography. Surgical pathology revealed occult invasive cancer in 278 (40%) women and 18 (3%) had axillary metastasis. Women with occult invasive cancer showed higher abnormality scores on AI-CAD than women with pure DCIS (mean, 70% vs. 51%; P < .001), and women with axillary metastasis had higher abnormality scores on AI-CAD than women without axillary metastasis (mean, 88% vs. 58%; P = .002). High ( >75%) abnormality score on AI-CAD (Odds ratio [OR], 1.8 [95% CI: 1.3, 2.6]; P < .001), age of 55 years or higher (OR, 1.6 [95% CI: 1.2, 2.3]; P =.005), present symptoms in the ipsilateral breast (OR, 2.7 [95% CI: 1.9, 4.0]; P < .001), biopsy performed with a 14-gauge automated gun (OR, 2.5 [95% CI: 1.7, 3.6]; P < .001), and high-grade DCIS at biopsy (OR, 2.5 [95% CI: 1.7, 3.5]; P < .001] were independent predictors of occult invasive cancer with a C-index of 0.75 (95% CI: 0.72, 0.78). Conclusion: The quantitative score of preoperative mammography obtained from a commercially available AI-CAD was able to predict occult invasive cancer in an easy and simple manner. AI-CAD applications for preoperative mammography may be useful in predicting occult invasive cancer in women with biopsy-proven DCIS, especially in those without preoperative breast MRI. Citation Format: Su Hyun Lee, Hajung Kim, Su Min Ha, Soo-Yeon Kim, Jung Min Chang, Nariya Cho, Woo Kyung Moon. Artificial Intelligence-based Computer-aided Diagnosis for Mammography: Predicting Occult Invasive Cancer in Women with Biopsy-proven Ductal Carcinoma in Situ [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 PO2-28-07.

Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer in a Nigerian Cohort

Background: Pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) is a marker for important clinical outcomes in the management of breast cancer. In Nigeria where the majority of patients are candidates for NAC, there is limited data on pCR following NAC. This study evaluated the pCR rate in a cohort of Nigerian patients. Methods: A retrospective review of patients who had NAC and mastectomy for breast cancer between 2017 and 2022. Relevant baseline clinicopathological and treatment data were obtained, pCR was defined as the absence of invasive cancer with or without in situ disease in the breast. The relationship between receptor status, type of chemotherapy and pCR was evaluated. Results: One hundred and sixty six of the 250 patients who had mastectomy during the period had NAC and were eligible for analysis. The mean age was 50.1±11.1, the majority had stage 3 disease. Overall (pCR) rate was 19.9% with the latter part of the study corresponding to the period with increased use of taxanes, having higher pCR (35.9% in 2022 vs 7.4% in 2017, p=0.024). Patients with HER 2 positive/Hormone receptor negative (HER 2+/HR-), HER 2+/HR+ and triple negative disease had significantly higher pCR than those with HR+/HER 2 negative disease (38.9%, 30.8%, 24.5% and 6.5% respectively, p=0.03). Conclusion: NAC resulted in pCR in about one-fifth of the entire cohort, particularly those with potentially aggressive HER 2+ and triple negative disease. The use of taxanes was associated with higher pCR rates.

Racial Disparities in Pathological Complete Response Among Patients Receiving Neoadjuvant Chemotherapy for Early-Stage Breast Cancer

Among patients with breast cancer, inconsistent findings have been published on racial disparities in achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT). To investigate whether racial disparities exist in achieving pCR and what factors contribute to them. Within the ongoing Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), which consists of a prospectively ascertained cohort of patients with breast cancer, 690 patients with stage I to III breast cancer receiving NACT were identified for this single-institution study at the University of Chicago Medicine. Patients diagnosed between 2002 and 2020 (median follow-up: 5.4 years) were included; next-generation sequencing data on tumor-normal tissue pairs were available from 186 ChiMEC patients, including both primary and residual tumor samples. Statistical analysis was performed from September 2021 to September 2022. Demographic, biological, and treatment factors that could contribute to disparities in achieving pCR. pCR was defined as the absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ. The study included 690 patients with breast cancer, with a mean (SD) age of 50.1 (12.8) years. Among the 355 White patients, 130 (36.6%) achieved pCR compared to 77 of the 269 Black patients (28.6%; P = .04). Not achieving pCR was associated with significantly worse overall survival (adjusted hazard ratio, 6.10; 95% CI, 2.80-13.32). Black patients had significantly lower odds of achieving pCR compared with White patients in the hormone receptor-negative/ERBB2+ subtype (adjusted odds ratio, 0.30; 95% CI, 0.11-0.81). Compared with White patients with ERBB2+ disease, Black patients were more likely to have MAPK pathway alterations (30.0% [6 of 20] vs 4.6% [1 of 22]; P = .04), a potential mechanism of anti-ERBB2 therapy resistance. Tumor mutational burden and somatic alterations in several genes (eg, FGF4, FGF3, CCND1, MCL1, FAT1, ERCC3, PTEN) were significantly different between the primary and residual tumors. In this cohort study of patients with breast cancer, racial disparities in response to NACT were associated with disparities in survival and varied across different breast cancer subtypes. This study highlights the potential benefits of better understanding the biology of primary and residual tumors.

Abstract GS5-01: Addition of platinum to sequential taxane-anthracycline neoadjuvant chemotherapy in patients with triple-negative breast cancer: A phase III randomized controlled trial

Abstract Background: Despite several studies, the impact of adding platinum on long-term outcomes in triple-negative breast cancer (TNBC) has not been definitively established. We conducted a single-centre randomized phase III trial to evaluate the efficacy and toxicity of adding platinum to standard neoadjuvant chemotherapy in these patients. Methods: Patients with histopathological diagnosis of TNBC without evidence of distant metastases who were planned to be treated with neoadjuvant chemotherapy (NACT) were randomized to experimental or control arms after stratification by menopausal status (premenopausal or perimenopausal, and postmenopausal) and stage [operable breast cancer (OBC, clinical T1-3, N0-1, M0), and locally advanced breast cancer (LABC, cT4 or N2-3, M0)]. NACT in control arm included paclitaxel 100 mg/m2 once per week for 8 weeks followed by doxorubicin (60 mg/m2) or epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) once every 21 days for 4 cycles while in experimental arm carboplatin (area-under-curve 2) was added once per week for 8 weeks with paclitaxel. After NACT patients received standard surgery for primary tumor and axillary lymph nodes (LN) followed by radiotherapy. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS), pathological complete response (pCR, absence of invasive cancer from breast and LN), and toxicity. Results: Between April 2010 and January 2020, 720 (355 control, 365 experimental) patients with a median age of 46 (25-69) years [< 50 years, 502 (69.7%), premenopausal 418 (58.2%)], were included in the study, of whom 285 (39.6%) had OBC and 435 (60.4%) had LABC, with a median clinical tumor size of 6.0 (1.2- 20.0) cm. At a median follow-up of 67.6 (18.9-142.2) months, in the experimental and control arms, the 5-year DFS were 70.6% (95% CI 65.7-75.5%) and 64.5% (95% CI 59.4-69.6%), respectively (HR 0.79, 95% CI 0.61-1.02, p=0.073), 5-year OS were 74.0 (95% CI 69.3-78.7%) and 66.7% (95% CI 61.6-71.8%), respectively (HR 0.75, 95% CI 0.57-0.98, p=0.034), and pCR were 55.2% (95% CI 49.7-69.5%) and 41.5% (95% CI 36.2-47.0%), respectively (p=0.0004). In subgroup analyses, the benefit of carboplatin was confined to patient’s < 50 years, with significant interaction between treatment and age. In women < 50 years of age, in experimental versus control arms, 5-year DFS and OS were 74.5% vs 62.3% (p=0.003, interaction p=0.003) and 76.8% vs 65.7% (p=0.003, interaction p=0.004), respectively. Addition of carboplatin had a significant beneficial impact on OS after adjusting for baseline clinical tumor size and age in a Cox model (HR 0.75, 95% CI 0.58-0.98, p=0.038). In experimental and control arms, numbers of patients with any grade >/=3 toxicity were 140 (38.5%) and 107/355 (30.14%), respectively, (p=0.02), grade >/=3 neutropenia were 2/364 (0.55%) and 1/355 (0.28%), respectively, grade >/=3 thrombocytopenia were 1/364 (0.27%) and 0 (0%), respectively, and febrile neutropenia were 26/364 (7.14%%) and 18/355 (5.07%), respectively (p=0.25). Conclusions: This study, to our knowledge the largest reported trial of neoadjuvant platinum in TNBC thus far, suggests that addition of carboplatin to sequential taxane-anthracycline neoadjuvant chemotherapy results in substantial and clinically meaningful improvement in disease-free and overall survival in young patients with TNBC and should be the standard of care in these patients. Citation Format: Sudeep Gupta, Nita S. Nair, Rohini Hawaldar, Vaibhav Vanmali, Vani Parmar, Seema Gulia, Jaya Ghosh, Shalaka Joshi, Rajiv Sarin, Tabassum Wadasadawala, Tejal Panhale, Sangeeta Desai, Tanuja Shet, Asawari Patil, Garvit Chitkara, Sushmita Rath, Jyoti Bajpai, Meenakshi Thakkur, Rajendra Badwe. Addition of platinum to sequential taxane-anthracycline neoadjuvant chemotherapy in patients with triple-negative breast cancer: A phase III randomized controlled trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS5-01.

Effects of enhancer of zeste homolog 2 and mucin 1 expressions on treatment response in breast cancer

Breast cancer is the most common malignancy in women. In the treatment of these patients, pathological complete response is defined as the absence of invasive cancer in breast or lymph node tissue after the completion of neoadjuvant chemotherapy. In this study, we aimed to investigate the relationship of enhancer of zeste homolog 2 and mucin 1 expressions with pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy. A total of 151 patients were included in the study. Enhancer of zeste homolog 2 and mucin 1 expressions were evaluated in the biopsy materials pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy surgical material, and their relationship with pathological complete response was investigated. The pathological complete response rates were significantly higher among the hormone receptor-negative patients, those with a high Ki-67 score, and patients with HER2-positive. Higher pathological complete response rates were obtained from patients with enhancer of zeste homolog 2 expression positivity pre-neoadjuvant chemotherapy. In addition, after neoadjuvant chemotherapy, enhancer of zeste homolog 2 expression was found to be completely negative in materials with pathological complete response; that is, in breast tissues considered to be tumor-free. While there was no significant relationship between mucin 1 expression and pathological complete response pre-neoadjuvant chemotherapy, mucin 1 expression was determined to significantly differ between the tissues with and without pathological complete response among the surgical materials examined. In our study investigating the relationship between enhancer of zeste homolog 2 and mucin 1 expression and pathological complete response in patients who received neoadjuvant chemotherapy, we found that enhancer of zeste homolog 2 expression could be used as a predictive marker for pathological complete response. However, mucin 1 expression was not associated with pathological complete response.

Factors associated with radiologic-pathologic discordance in magnetic resonance imaging after neoadjuvant chemotherapy for breast cancer

BackgroundAlthough breast MRI is known to be the best imaging modality for assessing the response after neoadjuvant chemotherapy (NAC), discordance still remains between MRI findings and final pathology findings. PurposeTo evaluate imaging and clinicopathologic factors associated with radiologic-pathologic discordance in breast cancer patients after NAC. Material and methodsThis retrospective study included 104 breast cancer patients (mean age: 50.2 years) who underwent breast MRI examinations before and after NAC between June 2015 and December 2019. Radiologic complete response (rCR) was defined as equal or lesser enhancement compared with breast tissue in post-NAC MRI. Pathologic CR (pCR) was defined as absence of invasive cancer in final pathology. Imaging and clinicopathologic factors associated with radiologic-pathologic discordance were analyzed with logistic regression analysis. ResultsOverall rCR and pCR rates were 37.5% (39/107) and 40.2% (43/107), respectively. Multivariate analysis revealed that the presence of non-mass enhancement (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.1–11.2; P = 0.03) and multicentric lesions on pre-NAC MRI (OR, 4.2; 95% CI, 1.2–14.9; P = 0.03) were independently associated with radiologic-pathologic discordance. False-positive rate for predicting residual tumor was the most prevalent in HER2-positive cancers (86.7%). ConclusionWhen determining rCR, the presence of non-mass enhancement and multicentric lesions on pre-NAC MRI, and HER2-positive cancers should be interpreted with caution.

Abstract OT1-12-04: A phase 3, open-label trial of neoadjuvant trastuzumab deruxtecan (T-DXd) monotherapy or T-DXd followed by THP compared with ddAC-THP in patients with high-risk HER2-positive early-stage breast cancer (DESTINY-Breast11)

Abstract Background: The current standard of care (SOC) for neoadjuvant treatment of human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer (EBC) consists of trastuzumab + pertuzumab and polychemotherapy. These multiagent regimens expose patients to short- and long-term toxicities, and many patients, particularly those with locally advanced or inflammatory disease, still experience relapse and/or death. In the phase 2 DESTINY-Breast01 study, T-DXd monotherapy demonstrated efficacy, with a confirmed objective response rate of 61.4% (complete response, 6.5%), median time to response of 1.6 months, and median progression-free survival of 19.4 months in patients with previously treated HER2-positive unresectable/metastatic breast cancer (Modi et al. SABCS 2020. Abstract PD3-06). Given the efficacy of T-DXd monotherapy, it is anticipated that replacing all or part of these SOC regimens with T-DXd could benefit patients with high-risk HER2-positive EBC. Here, we describe a phase 3 trial evaluating the efficacy, safety, and tolerability of T-DXd monotherapy or T-DXd followed by paclitaxel + trastuzumab + pertuzumab (THP) vs dose-dense doxorubicin + cyclophosphamide followed by THP (ddAC-THP) in patients with high-risk HER2-positive EBC. Methods: DESTINY-Breast11 is a phase 3, global, open-label, multicenter trial to determine the efficacy and safety of T-DXd monotherapy or T-DXd followed by THP as neoadjuvant treatment vs ddAC-THP in patients with high-risk (T stage ≥3 and/or node positive or inflammatory) HER2-positive EBC. Approximately 624 patients will be randomized 1:1:1 into 3 arms (arm A: T-DXd monotherapy every 3 weeks [q3w] for eight 3-week cycles; arm B: T-DXd [q3w for four 3-week cycles] followed by THP [paclitaxel every week + trastuzumab + pertuzumab q3w for four 3-week cycles]; arm C: ddAC-THP [ddAC every 2 weeks for four 2-week cycles followed by THP for four 3-week cycles]), stratified by hormone receptor status (positive vs negative) and central HER2 immunohistochemical score (IHC; IHC 3+ vs other). Patients should undergo breast or axillary surgery 3 to 6 weeks after administration of the last cycle of assigned treatment. After surgery, patients will receive treatment per local clinical standards. For patients who achieve a pathological complete response (pCR), adjuvant HER2-directed therapy for up to 1 year is recommended. For patients who do not achieve a pCR, therapy with up to 14 cycles of trastuzumab emtansine is recommended. Radiotherapy and endocrine therapy should be administered per local clinical standards. After the last dose of study treatment, patients will be assessed for survival and recurrence every 3 months for the first 3 years and every 6 months in years 4 and 5. The primary endpoint is pCR (ypT0/Tis ypN0) (defined as absence of invasive cancer in the breast and sampled regional lymph nodes) by central review. Secondary endpoints include pCR (ypT0 ypN0) (defined as absence of invasive and in situ cancer in the breast and sampled regional lymph nodes) by central review as well as 3-year event-free survival, 3-year invasive disease-free survival, overall survival, patient-reported tolerability, physical functioning, immunogenicity, pharmacokinetics, and safety. Exploratory endpoints include 3-year distant metastasis-free survival, objective response rate, rate of breast-conserving surgery, biomarkers, patient-reported outcomes, and healthcare resource utilization. Citation Format: Nadia Harbeck, Jean-François Boileau, Shanu Modi, Catherine M Kelly, Shinji Ohno, Jiong Wu, Mark Brekenridge, Pia Herbolsheimer, Tinghui Yu, Lajos Pusztai. A phase 3, open-label trial of neoadjuvant trastuzumab deruxtecan (T-DXd) monotherapy or T-DXd followed by THP compared with ddAC-THP in patients with high-risk HER2-positive early-stage breast cancer (DESTINY-Breast11) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-12-04.

Abstract LB063: Plasma cell-free DNA integrity predicts the achievement of pathological complete response to neoadjuvant chemotherapy in breast cancer patients

Abstract Background: Locally advanced breast cancer (BC) is currently treated with neoadjuvant chemotherapy (NACT) followed by surgery. NACT is able to achieve about a 20% rate of pathological complete response (pCR), defined as the absence of invasive cancer in breast and in axillary nodes. To date the pre-surgical assessment of clinical complete response (cCR) is mostly based, even though with suboptimal accuracy, on magnetic resonance imaging (MRI). Knowledge of cCR is useful to guide the surgical management of post-NACT BC. The study of plasma cell-free DNA integrity (DI) has shown serious potential for providing useful information in neoplastic patients in regard to early diagnosis, recurrence, and response to therapy. The aim of the present study is to estimate the accuracy of an electrophoresis-based method for DI assessment in the evaluation of the response to the systemic treatment in BC patients undergoing NACT. Methods: 62 BC patients undergoing anthracycline/taxane based NACT followed by surgery were recruited. Plasma samples were collected from each patient at diagnosis (T0), after anthracycline administration (T1), and after NACT completion before surgery (T2). After cfDNA extraction, cfDNA fragmentation profiling (DFP) was performed for each sample by automated electrophoresis on an Agilent Tapestation 2200 device. The concentration of differently sized cfDNA fragments, respectively of 90-150 base pairs (bp), 150-220 bp, 221-320 bp, 100-300 bp, and 321-1000 bp was assessed. cfDNA fragments size ranges evaluated as the most informative of the response to NACT were finally selected to calculate a normalized measure of DI, namely cfDNA integrity index (DII), expressed as the ratio of 321-1000 bp sized fragments concentration to 150-220 bp sized fragments one. DII was finally used to build an explorative classifier for BC response to NACT, directly comparing its performance with MRI, via bootstrapped logistic regression. Results: After preliminary essays to identify the most promising time point, DFP was performed on 38 plasma samples collected from as many patients at T2, with a 70/30 ratio between pCR and non pCR patients. DII showed an overall accuracy in correctly predicting the achievement of pCR of 81.6, with a cutoff above 2.71 having sensitivity = 81.8 and specificity = 81.5. MRI overall accuracy in the same cohort amounted to 77.1, with a sensitivity and a specificity of 72.7 and 81.5 respectively. The performance of the two techniques combined, in case of concordance, achieved an overall accuracy of 92.6 with a predictive value of complete response of 87.5 and a predictive value of absence of complete response of 94.7. Conclusions: DII measured before surgery after NACT completion shows great potential to correctly predict the achievement of pCR in BC patients. The evaluation of its use in combination with MRI is warranted in prospective studies. Citation Format: Gabriella Cirmena, Lorenzo Ferrando, Francesco Ravera, Anna Garuti, Valentina Barbero, Fabio Ferrando, Piero Fregatti, Lucia Del Mastro, Alessandro Garlaschi, Daniele Friedman, Alberto Ballestrero, Gabriele Zoppoli. Plasma cell-free DNA integrity predicts the achievement of pathological complete response to neoadjuvant chemotherapy in breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB063.

Better overall survival in patients who achieve pathological complete response after neoadjuvant chemotherapy for breast cancer in a Chilean public hospital.

IntroductionThere is extensive evidence associating the response to neoadjuvant chemotherapy (NeoCT) with breast cancer (BC) survival. However, to the author’s knowledge, there is no published data in Chile. The objective of the study is to evaluate whether achieving pathological complete response (pCR) after NeoCT is associated with greater survival and lower risk of recurrence in a Chilean Public Health Service.MethodsRetrospective analysis of a database. Patients with a diagnosis of Stages I–III BC who received NeoCT between 2009 and 2019 were included. Clinical and pathological information were extracted from the clinical records. BC subtypes were defined using hormone receptor (HR) information (HR: oestrogen and/or progesterone) and epidermal growth factor type 2 (HER2), being divided into four groups: HR+/HER2−, HR+/HER2+, HR−/HER2+, HR-/HER2−. pCR was defined as the absence of invasive cancer in the breast and axilla (ypT0/is N0) after NeoCT.ResultsOf 3,092 patients, 17.2% received NeoCT. Of these, 40.2% corresponded to HR+/HER2−, 20.9% HR+/HER2+, 18.2% HR−/HER2+ and 20.7% HR−/HER2−. Overall, 24.8% achieved pCR, being the lowest for HR+/HER2− (10.3%) and the highest for HR−/HER2+ (53.2%). In the multivariable analysis, family history, HER2+ and type of chemotherapy were associated with a greater probability of pCR. With a median follow-up of 40 months, the overall survival and metastasis-free survival (MFS) at 3 years were greater for the group with pCR compared to that which did not achieve it (90.5% versus 76.7%, p = 0.03 and 88.5% versus 71.4%, p = 0.003, respectively). The multivariable analysis confirmed this finding. Brain MFS was similar in both groups.ConclusionNeoCT is associated with greater pCR in aggressive BC subtypes. In those, achieving pCR was associated with better survival in our study. To the author’s knowledge, this is the first study which evaluates the relation between pCR and BC subtypes in a Chilean public hospital.

Evaluation of Post-Neoadjuvant Chemotherapy Pathologic Complete Response and Residual Tumor Size of Breast Cancer: Analysis on Accuracy of MRI and Affecting Factors

목적신보강화학요법을 시행한 유방암 환자에서 병리학적 관해와 잔류 암의 크기를 평가하는 데 있어 유방자기공명영상의 정확도를 분석하고 이에 영향을 미치는 인자들이 무엇인지 알아본다.대상과 방법2010년부터 2017년까지 본원에서 신보강화학요법 후 수술을 시행한 88명의 유방암 환자를 대상으로 하였다. 병리학적 관해는 수술 병리 결과에서 침윤성 유방암이 발견되지 않는 것으로 정의하였고 자기공명영상과 병리 조직의 잔류 암 크기 차이는 최대 직경으로 비교하였다. 병리학적 관해 및 자기공명영상과 병리 조직에서의 잔류 암 크기 차이에 영향을 미치는 인자를 알아보기 위해 통계분석을 시행하였다.결과전체 환자의 10%가 병리학적 관해에 도달하였다. 자기공명영상으로 관해를 예측할 때의 정확도와 곡선하부면적은 각각 90.91%, 0.8017이었다. 신보강화학요법 시행 후 유방자기공명영상과 병리 조직에서 측정한 잔류 암의 크기는 매우 강한 연관성을 보였고(r = 0.9, p < 0.001), 특히 영상에서 단일 종괴로 보였던 병변에서(p = 0.047) 그러하였다. 자기공명영상과 병리 조직 간의 잔류 암 크기는 내강형(p = 0.023), 그리고 자기공명영상에서 다초점 종괴 및 비종괴성 조영증강을 보인(p = 0.047) 환자군에서 유의미하게 큰 차이를 보였다.결론자기공명영상은 유방암의 병리학적 완전 관해와 잔류 암 크기의 평가에 있어서 정확도가 높은 검사이다. 유방암 아형과 병변의 영상의학적 소견이 자기공명영상의 정확도에 영향을 미친다.

Abstract P1-10-01: Safety and efficacy of neoadjuvant metformin with trastuzumab and chemotherapy in women with HER2-positive early breast cancer: A randomized, open-label, multicenter, phase 2 trial

Abstract Background: Epidemiological, pre-clinical, and window-of-opportunity trials have suggested that the anti-diabetic drug metformin (MET) may have beneficial effects on breast cancer (BC). The clinical relevance of combining MET with current standards of care for first-line treatment of BC is unknown. We investigated the safety and efficacy of adding MET to neoadjuvant chemotherapy plus trastuzumab (TTZ) in patients with HER2-positive early BC. Methods: In a randomized, multicenter, open-label phase 2 study, women with operable, locally advanced, or inflammatory HER2+ BC were randomly assigned in a 1:1 ratio to receive daily MET (1,700 mg) for 24 weeks concurrently with 12 cycles of weekly paclitaxel plus TTZ followed by four cycles of fluorouracil, epirubicin, cyclophosphamide/3w plus TTZ (arm A) or equivalent sequential chemotherapy plus TTZ without MET (arm B), followed by surgery. Patients were stratified by age, extent of disease (cT2 cN0-1 vs ≥ T3 or ≥ N2), and hormone receptor (HR)-status. The intention-to-treat (ITT) safety population comprised all women who underwent randomization and received at least one treatment dose. Primary endpoint was the rate of pathological complete response (pCR) analyzed in the per-protocol (PP) efficacy population. pCR was defined as absence of invasive cancer in the breast and axillary nodes, irrespective of carcinoma in situ (ypT0/is ypN0). Results: From June 1, 2012 to March 17, 2016, 98 patients were assessed for eligibility at 10 centers in Spain. Of 84 (85.7%) patients who were randomized, 41 patients were allocated to arm A and 43 to arm B. The most common adverse effects (AEs) in the 79 ITT patients were fatigue, diarrhea, nausea, alopecia, sensory neuropathy, mucositis, neutropenia, and elevated AST/ALT. Most AEs were grades 1–2 (&amp;gt;90% in both arms). The most common AEs grade ≥3 were neutropenia (7/38 women in arm A and 5/41 women in arm B) and diarrhea (5 and 0, respectively). The number of serious AEs was 3 in arm A (none of them was deemed to be MET-related) and 2 in arm B. At week 12, one (2.9%) patient in arm A and 6 (15%) in arm B exhibited asymptomatic decreases in the left ventricular ejection fraction (LVEF). At week 24, none (0%) of the patients in arm A and 3 (7.9%) patients in arm B presented decreases of LVEF below 50% and &amp;gt;10% from baseline. Only one patient (2.7%) in arm B experienced symptomatic heart failure. The rates of breast-conserving surgery were 79.3% and 58.6% in PP arms A and B, respectively. Also, 19/29 PP patients in arm A (65.5%, 95% CI 47–80) had a pCR versus 17/29 PP patients (58.6%, 95% CI 41–74) in arm B (OR 1.34 [95% CI 0.46–3.89], p=0.589). The combined rates of pCR and near-pCR (ypT1aN0) were 79.3% in arm A and 72.4% in arm B. Significantly fewer pCR were noted for tumors that were HR-positive regardless of which arm the patients were randomized. Conclusion: The higher pCR rate in HER2+ BC patients receiving MET-containing neoadjuvant therapy and TTZ did not reach statistical significance. Evaluation of long-term outcome data such as 5-year disease-free survival and correlative biological studies are needed to evaluate the clinico-molecular relevance of these findings. Citation Format: Pernas S, Dorca J, Álvarez-López I, Martínez S, Saura C, Batista López N, Rodríguez-Sánchez CA, Amillano K, Domínguez-Fernández S, Luque Cabal M, Morilla I, Viñas G, Cortés J, Cuyàs E, Verdura S, Fernández-Arroyo S, Joven J, Pérez E, García M, Bosch N, López-Bonet E, Saidani S, Buxó M, Menendez JA, Martin-Castillo B. Safety and efficacy of neoadjuvant metformin with trastuzumab and chemotherapy in women with HER2-positive early breast cancer: A randomized, open-label, multicenter, phase 2 trial [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 P1-10-01.

Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial

BackgroundWe have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown.Patients and methodsThe ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed.ResultsOf the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78–4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24–3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033–0.31; P < 0.001).ConclusionsLymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients.ClinicalTrials.govNCT01093235.

Abstract P5-16-20: Impact of “immunohistochemistry-based molecular subtype” on chemo-sensitivity and survival in Hispanic breast cancer patients following neoadjuvant chemotherapy (NAC)

Abstract NAC it´s the standard procedure when handling non-surgical tumors and inflammatory breast carcinomas, increases the possibility of conservative surgery and must be considered an evaluative tool in designing a therapeutic strategy. NAC improves Disease-Free Survival (DFS) and Overall Survival (OS) in patients achieving pathological complete response (pCR). “Immunohistochemitry-Based Molecular Subtyping” (IMS) with ER, PR,HER2 and KI67 has shown good correlation with gene expression assays to identify Intrinsic Molecular Subtypes. The relationship between IMS, chemo sensitivity and survival is currently a matter of interest. Achieving pCR at the time of Surgery has been associated with a favorable prognosis. Objectives:to investigate the pathological response to NAC and its correlation with IMS, as well as its correlation with DFS and OS in patients who have undergone NAC. Methods: Women &amp;gt; 18 years old. treated with NAC and surgery at IDC (January 2009 to December 2013).Demographic, clinical en follow-up variables were obtained from de IDC patient´s registry. Patient´s vital status was traced trough phone calls.pCR was defined as ypT0 ypN0 (the absence of invasive cancer AND in situ cancer in the breast and axillary nodes). IDC´s IRB approved the research project. Results: A total of 592 patients fulfilled the study's inclusion criteria. The distribution by subtypes were: “Luminal A”: 150 (25.3%), “Luminal B/HER2 -”: 189 (31.9%), “Luminal B/HER2+”: 114 (19.3%), “HER2-enriched”: 45 (7.6%) and “Triple negative”: 94 (15.9%). The median follow-up was 51 months (interquartile range: 37-68).Pathological response to NAC was: complete pathological response (pCR) in 59 (10%) patients, partial pathological response in 426 (72.0%); stable disease in 82 (13.8%), and progression in 25 (4.2%) patients.In Multivariable Cox Regression Models, pCR is associated with a significant improvement in the DFS (HR 6.89; 95% CI: 2.53 to 18.75. p=0.01) and OS (HR 6.82; 95% CI 2.13 to 21.78. p=0.01). By “Immunohistochemistry-based molecular subtype” the pCR is associated with a significantly better DFS for “Luminal B”, “Triple Negative” and “HER2-enriched”. For OS we found significantly association with pCR for “Triple negative” and “”Luminal B” “Immunohistochemistry-based molecular subtype”. The “HER2-enriched”shown a trend to better OS if obtain pCR (p=0.05). Conclusions: pCR is associated with an improved overall survival and disease-free survival rates in this group of Hispanics patients. In advanced stages, histologial grade 3, Luminal B, Triple Negative and HER2+ enriched tumors the pCR is associated with a significantly better DFS . Citation Format: Gomez-Wolff R, Garcia H, Ossa C. Impact of “immunohistochemistry-based molecular subtype” on chemo-sensitivity and survival in Hispanic breast cancer patients following neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-20.

OP1-4 - Predictive factors of invasive breast cancer recurrence for patients achieving pCR after neoadjuvant chemotherapy

Background: Breast Cancer patients who achieved pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) had a reduced risk of death compared with those who did not. However, the risk factors for relapse after achieving pCR are not well defined. Methods: Consecutive breast cancer patients who had definitive surgery following NAC between 6/2004 and 12/2013 at National Cancer Center Hospital East were retrospectively reviewed. A pCR was defined as an absence of invasive cancer in the breast and axillary nodes. Patient characteristics and clinicopathological features were collected from medical records. An immunohistochemistry (IHC) based subtype was assigned based on St. Gallen criteria; Luminal type, Luminal HER2, HER2 enriched, and triple negative. We utilized hormone receptor positive cut-off was 1.0%. Correlations between these factors and relapses were analyzed. Results: Among 564 breast cancer patients, 110 achieved pCR. Median age was 55.5 (26-75) years old with median follow up of 54.5 months (9-122). 10 patients (9.1%) experienced invasive breast cancer recurrence and 9 out of 10 were HER2-positive. The first distant recurrent sites were brain (4 cases), liver (2 cases), and bones (1 case). HER2, axillary lymph nodes metastases, clinical stage, subtype and BMI (>22) were significantly correlated (p <0.05) with recurrence in the univariate analyses. HER2-positive (HR 23.68, 95% CI; 2.060-272.3), higher BMI (HR 9.685, 95% CI; 1.505-62.34), and cN3 (HR 50.02, 95% CI; 4.001-625.3) were significantly correlated with relapse in the multivariate analyses. Conclusion: Patients with HER2-positive, higher BMI, and advanced nodal involvement are at high risk for invasive breast cancer relapse even if they have achieved pCR. Background: Breast Cancer patients who achieved pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) had a reduced risk of death compared with those who did not. However, the risk factors for relapse after achieving pCR are not well defined. Methods: Consecutive breast cancer patients who had definitive surgery following NAC between 6/2004 and 12/2013 at National Cancer Center Hospital East were retrospectively reviewed. A pCR was defined as an absence of invasive cancer in the breast and axillary nodes. Patient characteristics and clinicopathological features were collected from medical records. An immunohistochemistry (IHC) based subtype was assigned based on St. Gallen criteria; Luminal type, Luminal HER2, HER2 enriched, and triple negative. We utilized hormone receptor positive cut-off was 1.0%. Correlations between these factors and relapses were analyzed. Results: Among 564 breast cancer patients, 110 achieved pCR. Median age was 55.5 (26-75) years old with median follow up of 54.5 months (9-122). 10 patients (9.1%) experienced invasive breast cancer recurrence and 9 out of 10 were HER2-positive. The first distant recurrent sites were brain (4 cases), liver (2 cases), and bones (1 case). HER2, axillary lymph nodes metastases, clinical stage, subtype and BMI (>22) were significantly correlated (p <0.05) with recurrence in the univariate analyses. HER2-positive (HR 23.68, 95% CI; 2.060-272.3), higher BMI (HR 9.685, 95% CI; 1.505-62.34), and cN3 (HR 50.02, 95% CI; 4.001-625.3) were significantly correlated with relapse in the multivariate analyses. Conclusion: Patients with HER2-positive, higher BMI, and advanced nodal involvement are at high risk for invasive breast cancer relapse even if they have achieved pCR.

Abstract CT091: A neoadjuvant co-clinical trial in triple-negative breast cancer patients with genomic discovery analysis

Abstract Background: Patients with TNBC who do not achieve a pathologic complete response (pCR) or near pCR have high rates of relapse, due to chemotherapy resistance, within the first few years after their diagnosis. Molecular biomarkers predictive for chemotherapy sensitivity are lacking. This ongoing trial is evaluating carboplatin and docetaxel in the neoadjuvant setting to determine whether these drugs will increase the pCR rate compared to historical controls. Correlative studies include exome and transcriptome sequencing on samples acquired from patients as a means to decipher the genomic architecture and clonal evolution of those who achieved a pCR compared to those who did not. The simultaneous development of patient derived xenografts (PDX) from host tumors is also planned. Methods: Patients with clinical stage 2 or 3 histologically confirmed TNBC will receive six cycles of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 every 3 weeks, followed by definitive surgery. Forty-one eligible patients will be treated according to this protocol, permitting us to attain a power of 83% to detect our expected pCR rate of 54% compared to the historical 35% rate, based on a two-sided exact binomial test at the 4.8% significance level. Eligibility: tumor size at least 2 cm, adequate organ and bone marrow function, no bilateral or inflammatory breast cancer, no invasive cancer within 5 years, ECOG performance status of ? 2, no prior sentinel lymph node biopsy. Tissue collection for xenografting and correlative studies will occur at baseline, at cycle 1 day 3, and at surgery. The primary objective is to determine the pCR rate, defined as the absence of invasive cancer in breast or nodes at definitive surgery. Secondary and exploratory objectives include xenografting rates, evaluation of mutational signatures of chemotherapy resistance and response, and comparison of chemotherapy responses between patients and their xenografts. The study was activated on 7/7/2014 and is still recruiting. Twenty (48.8% of planned 41) patients have been enrolled and have had baseline tissue banked. Fourteen patients have completed protocol therapy. Three patients have tissue at all 3 time points (9 samples), and are presently being studied by exome and transcriptome sequencing. Citation Format: Foluso O. Ademuyiwa, Shunqiang Li, Jingqin Luo, Tracy Skinner, Jason Hoshower, Cynthia X. Ma, Katherine Weilbaecher, Michael Naughton, Leonel Hernandez-Aya, Elaine R. Mardis, Matthew J. Ellis. A neoadjuvant co-clinical trial in triple-negative breast cancer patients with genomic discovery analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT091.

Evaluation of pretherapeutic Ki67 as predictive marker for response to neoadjuvant chemotherapy in patients with primary breast cancer.

e12500Background: The proliferation marker Ki67 is an established prognostic and predictive marker in breast cancer. The association between Ki67 and treatment response in the neoadjuvant setting, however, is still unclear. We have therefore evaluated whether Ki67 can predict pathological complete response (pCR) in women with neoadjuvant chemotherapy (NAC). Methods: We included prospectively collected data of women with primary breast cancer who underwent NAC from 2005–2015 at the Medical University of Vienna, Department of Gynecology. Chemotherapy consisted of 4 cycles epirubicin (90 mg/m2, q3w), followed by 4 cycles docetaxel (100 mg/m2, q3w), which was co-administered with trastuzumab in HER2-positive tumors. Ki67, hormone receptor and HER2-status were examined by immunohistochemistry using core needle biopsy specimens obtained prior to NAC. NAC-related effects were evaluated in surgical specimen; pCR was defined as the absence of invasive cancer in breast and axillary nodes. Results: A total of 95 wom...

Abstract P5-01-02: Multimodality molecular imaging with dynamic 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and MRI to evaluate response and resistance to neoadjuvant chemotherapy (NAC)

Abstract Background: Using quantitative FDG PET to measure glucose metabolism and perfusion, and dynamic contrast-enhanced (DCE) MRI to measure perfusion, we previously identified a metabolic signature for breast cancer resistant to NAC. This imaging signature is (1) persistent or increased tumor perfusion despite treatment, (2) an altered pattern of glucose kinetics in response to therapy, and (3) pre-therapy mismatch between tumor metabolism (MRFDG) and glucose delivery (K1) (high ratio of MRFDG/K1). These patterns predict poor response, early relapse and death independent of established prognostic factors, including pathologic response. Identification of factors associated with resistance or response to therapy is the translational goal of "Quantitative Dynamic PET and MRI in Breast Cancer Therapy," part of the Seattle Breast SPORE (1P50CA138293). Methods: Patients (Pts) undergoing NAC for histologically confirmed breast cancer (stage II-III) were approached for this trial (CCIRB# 7587). FDG PET and DCE-MRI were obtained pre-therapy, 2-12 weeks after start of NAC (mid-therapy) and after completion of NAC. Breast biopsies were obtained pre-therapy and post-NAC. FDG PET included a dynamic scan with kinetic analysis. PET measures included SUVmax, MRFDG, K1, Ki, and Patlak. 3T DCE-MRI measurements included semi-quantitative vascular parameters of peak enhancement (PE), signal enhancement ratio (SER), washout fraction, functional tumor volume, and apparent diffusion coefficient (ADC) from diffusion-weighted MRI (DWI). Breast biopsies were assayed by immunohistochemistry and gene expression profiling. NAC was per physician's choice with most pts receiving weekly paclitaxel (with trastuzumab if HER2+) followed by doxorubicin/cyclophosphamide. Results: 32 pts have completed the study. Pathologic complete response (pCR), defined as absence of invasive cancer in the breast, was observed in 9 (28%); near pCR defined as only microscopic residual invasive cancer in 3 (9%) more pts. Mid-therapy decline in SUVmax and K1 was associated with near pCR; (p-value 0.06, 0.04, respectively). Pre-therapy PET measures of MRFDG and K1 were not predictive of pCR. On MRI, pre-therapy PE (p=0.009), SER (p=0.01), washout fraction (p=0.02), ADC (p=0.08, trend) and mid-therapy change in volume (p=0.05) were each predictive of pCR. Gene profiling of pre-therapy biopsies showed correlation between high MRFDG/K1 ratio in basal and luminal B tumors. Conclusions: Assessment of serial changes in tumor metabolism and perfusion by FDG PET and DCE-MRI is feasible in the clinic. Mid-therapy decline in metabolism and glucose delivery was predictive of pCR; consistent with prior retrospective series. Baseline DCE-MRI and DWI measures show promise to predict response, and associations of mid-therapy change in MR functional tumor volume with pCR agree with findings of another multisite clinical trial (ISPY). These imaging parameters may serve as useful biomarkers to inform future neoadjuvant trials. Integration of imaging data with gene expression profiling revealed that the pattern of metabolism in luminal B tumors was closer to that of the basal subtype compared to other ER-positive tumors. Citation Format: Specht JM, Partridge S, Chai X, Novakova A, Peterson L, Shields A, Guenthoer J, Linden HM, Gralow JR, Gadi V, Korde L, Hills D, Hsu L, Hockenbery DM, Kinahan P, Mankoff DA, Porter PL. Multimodality molecular imaging with dynamic 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and MRI to evaluate response and resistance to neoadjuvant chemotherapy (NAC). [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 P5-01-02.

Endoscopic resection of advanced and laterally spreading duodenal papillary tumors.

Historically, neoplasia of the duodenal papilla has been managed surgically, which may be associated with substantial morbidity and mortality. In the absence of invasive cancer, even lesions with extensive lateral duodenal wall involvement, or limited intraductal extension may be cured endoscopically with a superior safety profile. Endoscopic papillectomy is associated with greater risks of adverse events such as bleeding than resection elsewhere in the gastrointestinal tract. Additionally site-specific complications such as pancreatitis exist. A structured approach to lesion assessment, adherence to technical aspects of resection, endoscopic management of complications and post-resection surveillance is required. Advances have been made in all facets of endoscopic papillary resection since its introduction in the 1980s; extending the boundaries of endoscopic cure, optimizing outcomes and enhancing patient safety. These will be the focus of the present review.