Neoadjuvant Treatment Of Breast Cancer Research Articles

FGFR1 Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer

HER2-positive breast cancer (BC) is an aggressive subtype that affects 20–25% of BC patients. For these patients, neoadjuvant therapy is a good option that targets a pathological complete response (pCR) and more breast-conserving surgery. In effect, the outcomes of patients with HER2-positive BC have dramatically improved since the introduction of anti-HER2 antibodies such as trastuzumab (TZ) and/or pertuzumab (PZ) added to chemotherapy. This study sought to examine whether correlation exists between copy number variations (CNVs) in several genes related to the PI3K/AKT pathway (HER2, FGFR1, PIK3CA, AKT3 and MDM2) and the efficacy of anti-HER2 neoadjuvant treatment in patients with early HER2-positive BC. Forty-nine patients received TZ or PZ/TZ and chemotherapy as neoadjuvant treatment. Gene CNVs were determined by quantitative polymerase chain reaction on paraffin-embedded biopsy specimens. The response to 6 months of therapy was assessed by Miller–Payne grading of the tumor on surgical resection; grades 4 and 5, indicating >90% tumor reduction, were defined as a good response. A good response was shown by 64.5% and a pCR by 31.2% of patients. When stratified by anti-HER2 antibody received and gene CNV, it was found that patients with FGFR1 gene amplification or those with FGFR1 amplification treated with TZ alone showed a poor response (p = 0.024 and p = 0.037, respectively). In the subset of patients treated with TZ/PZ combined, the pCR rate was significantly lower among those showing FGFR1 amplification (p = 0.021). Although based on a small sample size, our findings suggest that patients with FGFR1 amplification might benefit less from anti-HER2 antibody therapy.

Predictors of pathologic complete response to neoadjuvant treatment in HER2-overexpressing breast cancer: a retrospective analysis using real-world data

The human epidermal growth factor receptor 2 (ERBB2, HER2 or HER2/neu) is a transmembrane tyrosine kinase receptor that is overexpressed in approximately 20% of breast cancers. The use of the anti-HER2 monoclonal antibodies Pertuzumab and Trastuzumab in association with chemotherapy has achieved a higher percentage of pathologic complete response (pCR) than conventional chemotherapy. The purpose of our study was to identify factors that could affect the therapeutic response of patients with breast cancer and HER2 overexpression treated with cytotoxic chemotherapy plus double HER2 blockade in neoadjuvant setting at Fundación Arturo López Pérez (FALP). A case–control study was designed to evaluate the effect of clinical and histopathological variables on the response to neoadjuvant therapy. Ninety-four women with non-metastatic breast cancer and HER2 overexpression received neoadjuvant combination chemotherapy with Trastuzumab and Pertuzumab at FALP during the period 2017–2020. Seventy percent of patients achieved pCR, and in the group of hormone receptor negative patients, 89% of patients achieved pCR. Different variables were analysed trying to look for clinicopathological predictors of complete response. This study provides us with real-world data on the efficacy of using this treatment combination in our population of HER2-overexpressing breast cancer patients.

Expert consensus on neoadjuvant treatment of breast cancer in China (2021 edition)

Expert consensus on neoadjuvant treatment of breast cancer in China (2021 edition)

Real-world Research of Trastuzumab and Pertuzumab Combined with Chemotherapy in Neoadjuvant Treatment of HER2-positive Breast Cancer

Real-world Research of Trastuzumab and Pertuzumab Combined with Chemotherapy in Neoadjuvant Treatment of HER2-positive Breast Cancer

Effectiveness and safety of pegylated liposomal doxorubicin versus epirubicin as neoadjuvant or adjuvant chemotherapy for breast cancer: a real-world study

BackgroundPegylated liposomal doxorubicin (PLD) is an improved formulation of doxorubicin with comparable effectiveness but significantly lower cardiotoxicity than conventional anthracycline. This study aimed to evaluate the real-world effectiveness and safety of PLD versus epirubicin as neoadjuvant or adjuvant treatment for breast cancer.MethodsClinical data of invasive breast cancer patients who received neoadjuvant or adjuvant chemotherapy with PLD or epirubicin were retrospectively collected. Propensity score matching (PSM) was performed to reduce the risk of selection bias. The molecular typing of these patients included Luminal A, Luminal B, HER2-positive, and basal-like/triple-negative. The primary outcome was pathological complete response (pCR) rate for neoadjuvant chemotherapy and 3-year disease-free survival (DFS) rate for adjuvant chemotherapy. Noninferiority was suggested if the lower limit of the 95% CI for the 3-year DFS rate difference was greater than − 10%. The secondary outcome was adverse reactions.ResultsA total of 1213 patients were included (neoadjuvant, n = 274; adjuvant, n = 939). pCR (ypT0/Tis ypN0) rates of patients who received neoadjuvant chemotherapy were 11.6% for the PLD group and 7.0% for the epirubicin group, but the difference was not statistically significant (P = 0.4578). The 3-year DFS rate of patients who received adjuvant chemotherapy was 94.9% [95%CI, 91.1–98.6%] for the PLD group and 95.4% [95%CI, 93.0–97.9%] for the epirubicin group (P = 0.5684). Rate difference between the two groups and its 95% CI was - 0.55 [− 5.02, 3.92]. The lower limit of the 95% CI was − 5.0% > − 10.0%, suggesting that PLD is not be inferior to epirubicin in adjuvant chemotherapy for breast cancer. The incidences of myelosuppression, decreased appetite, alopecia, gastrointestinal reactions, and cardiotoxicity were lower in the PLD group than in the epirubicin group, while the incidence of nausea was higher in the PLD group.ConclusionsIn the neoadjuvant and adjuvant treatment of breast cancer, effectiveness is similar but toxicities are different between the PLD-containing regimen and epirubicin-containing regimen. Therefore, further study is warranted to explore PLD-based neoadjuvant and adjuvant chemotherapy for breast cancer.

MRI in the Setting of Neoadjuvant Treatment of Breast Cancer.

Neoadjuvant therapy may reduce tumor burden preoperatively, allowing breast conservation treatment for tumors previously unresectable or requiring mastectomy without reducing disease-free survival. Oncologists can also use the response of the tumor to neoadjuvant chemotherapy (NAC) to identify treatment likely to be successful against any unknown potential distant metastasis. Accurate preoperative estimations of tumor size are necessary to guide appropriate treatment with minimal delays and can provide prognostic information. Clinical breast examination and mammography are inaccurate methods for measuring tumor size after NAC and can over- and underestimate residual disease. While US is commonly used to measure changes in tumor size during NAC due to its availability and low cost, MRI remains more accurate and simultaneously images the entire breast and axilla. No method is sufficiently accurate at predicting complete pathological response that would obviate the need for surgery. Diffusion-weighted MRI, MR spectroscopy, and MRI-based radiomics are emerging fields that potentially increase the predictive accuracy of tumor response to NAC.

Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer

I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY’s prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.

Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer

Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials. To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival. The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate. Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery. Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS). A total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis. In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy. ClinicalTrials.gov Identifier: NCT01042379.

The addition of neoadjuvant pertuzumab for the treatment of HER2+ breast cancer: a cost estimate with real-world data

BackgroundBreast cancer (BC) is largely prevalent worldwide. HER2-positive BC account for roughly 20–25% of all BC cases and has an overall survival lower than other BC. Innovation on BC therapeutics is a constant, but novel therapies have higher costs. Therefore, cost-effectiveness research is essential to provide healthcare decision-makers with solid foundations for a resource allocation. This study aims to estimate the average direct medical costs/patient and cost-effectiveness of adding pertuzumab in neoadjuvant treatment (NeoT) for HER2-positive breast cancer (BC).MethodsTwo retrospective real-world consecutive cohorts of ≥18yo female patients diagnosed with HER2-positive BC treated with NeoT at the Breast Clinic of IPO-Porto were studied. The AC-DH regimen (2012–2015) comprised 8 cycles of neoadjuvant therapy (4 cycles of doxorubicin + cyclosphosphamide followed by 4 cycles ofdocetaxel + trastuzumab), while the AC-DHP regimen (2015–2017) included also pertuzumab as NeoT. NeoT was followed by surgery and adjuvant trastuzumab. Micro-costing technique and a bottom-up approach was used comprising all medical direct costs from the hospital perspective. Unit costs were obtained from government official prices or from IPO-Porto costing system. Costs were adjusted to 2017 and are expressed in euros. Multivariable logistic regression models were used for effectiveness assessment, while generalized linear models with gamma distribution were used for costs. ICER was calculated using the pathological complete response (pCR) as the preferential measure of effectiveness. Sensitivity analysis was also performed.ResultsAC-DHP (n = 40) and AC-DH (n = 54) cohorts had heterogenous patient profiles (median age 43y/53y; 67.5%/59.3% positive HR; 60.0%/27.8% operable; 25.0%/24.1% inflammatory, respectively). The AC-DHP average total cost/patient was 56,375€, with pertuzumab accounting for 13,978€ (24.79%) and increasing in 15,982€ the average cost/patient (p < 0.001). Clinical staging and hormone receptors (HR) were significantly associated with pCR. ICER was 1.370€ per percentage point of pCR.ConclusionsICER was more favourable in stage III HR negative BC patients compared to other patient profiles. Innovative treatments access is critical to deliver high-quality healthcare, but sustainability must be considered. These results suggest the importance of establishing a cost-effectiveness profile of Pertuzumab in NeoT for HER2-positive BC.

181P Pegylated liposomal doxorubicin (PLD) combined with docetaxel and trastuzumab in neoadjuvant treatment for HER2-positive breast cancer: A multicenter, randomized, phase II, open-label trial

Trastuzumab based chemotherapy is the standard regimen for HER2+ breast cancer (BC) in neoadjuvant trerapy. Combination of trastuzumab and anthracycline is generally avoided clinically due to the cardiotoxicity of the two drugs. PLD is less cardiotoxic compared with traditional anthracyclines. Here, we conducted this prospective study to evaluate the efficacy and safety of PLD (A) + docetaxel (T) + trastuzumab (H) in neoadjuvant treatment for HER2+ BC.

180P Relapse pattern after neoadjuvant treatment in early breast cancer

Neoadjuvant treatment is becoming established in early breast cancer due to its impact in overall survival. Although it is the Her2 and triple-negative phenotypes where the greatest impact has been seen, the luminal has also seen it, so it is interesting to find the patterns of recurrence after neoadjuvant treatment.

Aqueous Extract of Dacryodes edulis (Burseraceae) Leaves Inhibited Tumor Growth in Female Wistar Rats with 7,12-Dimethylbenz[a]anthracene-Induced Breast Cancer.

Breast cancer is the most common estrogen-dependent cancer in the world. Hormone therapy for this cancer can be neoadjuvant and/or adjuvant. Herbal remedies with antiproliferative properties are believed to be potential anticancer agents. The aqueous extract of Dacryodes edulis (Burseraceae) leaves (AE), a medicinal plant used against cancer in Cameroon, was found to display antiproliferative effects in ovariectomized rats. Compounds isolated from this plant exhibited anticancer activity in vitro. To determine whether AE has an anticancer potential, its effects were investigated in rats with already developed breast cancer. Mammary tumors were induced by a single subcutaneous administration (under the mammary gland) of 7,12-dimethylbenz[a]anthracene (DMBA; 50 mg/kgBW) to immature female rats. After 22–26 weeks of observation, animals with palpable tumors were treated with tamoxifen (3.3 mg/kgBW) and AE at doses of 25 and 100 mg/kgBW. The negative control received distilled water. Treatments were given orally for 21 consecutive days. The volume of mammary tumors was evaluated weekly using a caliper. On day 22, animals were sacrificed. Cholesterol and estradiol levels were assessed in serum, breast tumors, mammary glands, and ovaries. Oxidative status of tumors was evaluated. The histological analysis of mammary glands and breast tumors was performed. Results showed that AE reduced tumor volume and weight (p < 0.05). This effect was associated with reduced cholesterol (p < 0.001) and estradiol (p < 0.01) levels in breast tumors, serum, ovaries, and mammary glands. AE also increased tumors levels of malondialdehyde (p < 0.05) and antioxidant enzymes (p < 0.01). These effects contributed to the decrease in the size of breast alveoli (p < 0.01), the density of cancer cells in breast tumors, and the invasion of these cells into the tumor connective tissue. In conclusion, the aqueous extract of D. edulis leaves, thanks to its ability to inhibit tumor growth, could be considered as a potential alternative for the neoadjuvant treatment of estrogen-dependent breast cancer.

Feasibility of ABUS as an Alternative to Handheld Ultrasound for Response Control in Neoadjuvant Breast Cancer Treatment

IntroductionThe Invenia Automated Breast Ultrasound Screening (ABUS) is indicated as an adjunct to mammography for breast cancer screening in asymptomatic women with high-density breast tissue. ABUS provides time-efficient evaluation of the 3-dimensional recordings within 3 to 6 minutes. The role and advantages of ABUS in everyday clinical practice, especially in routine examination during neoadjuvant chemotherapy (NACT), is not clear. The aim of this monocentric, noninterventional retrospective study is to evaluate the use of ABUS in patients who are under NACT treatment for response control. MethodsRegular sonographic response check with handheld ultrasound (HHUS) examination and with ABUS were conducted in 83 women who underwent NACT. The response controls were conducted every 3 to 6 weeks during NACT. The handheld sonography was performed with GE Voluson S8. Handheld sonographic measurements and ABUS measurements were compared with the final pathologic tumor size. ResultsThere was no statistical difference between the measurements with HHUS examination or ABUS compared with final pathologic tumor size (P = .47). The average difference from ABUS measured tumor size to final pathologic tumor size was 9.8 mm. The average difference from handheld measured tumor size to final pathologic tumor size was 9/3 mm. Both the specificity of ABUS and HHUS examination in predicting pathologic complete remission was 100%. ConclusionABUS seems to be a suitable method to conduct response control in neoadjuvant breast cancer treatment. ABUS may facilitate preoperative planning and offers remarkable time saving for physicians compared with HHUS examination and thus should be considered for clinical practice

Pathologic response of ductal carcinoma in situ to neoadjuvant systemic treatment in HER2-positive breast cancer

PurposeThe presence of extensive ductal carcinoma in situ (DCIS) adjacent to HER2-positive invasive breast cancer (IBC) is often a contra-indication for breast-conserving surgery, even in case of excellent treatment response of the invasive component. Data on the response of DCIS to neoadjuvant systemic treatment (NST) are limited. Therefore, we estimated the response of adjacent DCIS to NST-containing HER2-blockade in HER2-positive breast cancer patients and assessed the association of clinicopathological and radiological factors with response.MethodsPre-NST biopsies were examined to determine presence of DCIS in all women with HER2-positive IBC treated with trastuzumab-containing NST ± pertuzumab between 2004 and 2017 in a comprehensive cancer center. When present, multiple DCIS factors, including grade, calcifications, necrosis, hormone receptor, and Ki-67 expression, were scored. Associations of clinicopathological and radiological factors with complete response were assessed using logistic regression models.ResultsAdjacent DCIS, observed in 138/316 patients with HER2-positive IBC, was eradicated after NST in 46% of patients. Absence of calcifications suspicious for malignancy on pre-NST mammography (odds ratio (OR) 3.75; 95% confidence interval (95% CI) 1.72–8.17), treatment with dual HER2-blockade (OR 2.36; 95% CI 1.17–4.75), a (near) complete response on MRI (OR 3.55; 95% CI 1.31–9.64), and absence of calcifications (OR 3.19; 95% CI 1.34–7.60) and Ki-67 > 20% in DCIS (OR 2.74; 95% CI 1.09–6.89) on pre-NST biopsy were significantly associated with DCIS response.ConclusionsAs DCIS can respond to NST containing HER2-blockade, the presence of extensive DCIS in HER2-positive breast cancer before NST should not always indicate a mastectomy. The predictive factors we found could be helpful when considering breast-conserving surgery in these patients.

63O Letrozole and palbociclib versus third generation chemotherapy as neoadjuvant treatment in luminal breast cancer: Survival results of the UNICANCER-NeoPAL study

The NeoPAL trial compared letrozole-palbociclib (LETPAL) combination to standard chemotherapy (CT) as neoadjuvant treatment in patients with high-risk LBC. Both LETPAL and CT were associated with poor pathological response, and equivalent clinical responses, while LETPAL let to encouraging biomarker responses in Prosigna®-defined high-risk LBC. We now evaluate the survival outcomes of both groups.

AB002. SOH21AS038. Optimal timing of surgery following breast cancer neoadjuvant chemotherapy: a systematic review and meta-analysis

Background: The indications for neoadjuvant breast cancer treatment have expanded rapidly in recent decades. Administration of chemotherapy before surgery has the potential to reduce the risk of distant recurrence by targeting circulating micrometastases as well as allowing a more minimalistic approach to surgical intervention. This study aimed to determine the optimum timing of surgery post breast cancer neoadjuvant chemotherapy (NACT).

Assisted computer and imaging system improve accuracy of breast tumor size assessment after neoadjuvant chemotherapy.

BackgroundThe use of neoadjuvant therapy (NAT) in patients with early breast cancer is becoming increasingly common. The purpose of this study was to explore the combined use of breast pathology cabinet X-ray system (CXS) to accurately assess the response to neoadjuvant treatment of breast cancer and establish a standard evaluation system.MethodsA total of 100 patients with breast cancer after neoadjuvant treatment were randomly selected. Preoperative imaging evaluation of tumor masses were significantly degenerated, and they were randomly divided into experimental and control groups of 50 cases each. Compared with the traditional two methods of material extraction, the effective material extraction rate is comparative. Take the two largest diameters of the largest two-dimensional surface of the tumor bed as the measurement object, the macro-description value is D1/D2, the radiographic system description measurement value is the experimental group d1/d2, and the correction under the microscope is worth the true size of the tumor bed H1/H2 as the final test standard, calculate the difference between D1/D2 and d1/d2 with H1 and H2, and compare the difference between d1− H1, d2 − H2 and D1− H1, D2 − H2.ResultsThe average group of tissue samples in the experimental group was 16.4, and the average group of tissue samples in the control group was 16.7, and there was no difference between the two groups; The effective tissue blocks of tumor bed samples in the experimental group were11.8, and the control group was 7.5. There is difference between the two groups. The average effective percentage of tumor bed in the experimental group was 72%, and the average effective percentage of tumor bed in the control group was 44.8%. The difference was also statistically significant; d1− H1, d2 − H2 and D1− H1, D2 − H2 are all different.ConclusionsCXS assists the collection of breast tumor bed, which can significantly improve the efficiency of tumor bed collection and save the cost of collection. Compared with the maximum diameter of the tumor bed by eyes, the CXS mapping value is closer to the value measured under the microscope.

Abstract PS12-03: Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment in luminal breast cancer: Survival results of the UNICANCER-NeoPAL study

Abstract Background Palbociclib is a CDK4/6 inhibitor with demonstrated survival benefits in combination with endocrine therapy in advanced luminal breast cancer (LBC). Its potential role in early breast cancer is currently explored. The NeoPAL trial compared letrozole-palbociclib (LETPAL) combination to standard chemotherapy (CT) as neoadjuvant treatment in patients with high-risk LBC. Both LETPAL and CT were associated with poor pathological response, and equivalent clinical responses, while LETPAL let to encouraging biomarker responses in Prosigna®-defined high-risk LBC. We now evaluate the survival outcomes of both groups. Patients and Methods NeoPAL (UCBG10/4, NCT02400567) is a randomized, parallel, non-comparative phase II study. Postmenopausal women with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II-III breast cancer, not candidate for breast-conserving surgery, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks (LETPAL), or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) x3 21-day courses followed by docetaxel 100 mg/m2 x3 21-day courses (CT). Secondary endpoints included progression-free survival (PFS) and invasive-disease free survival (iDFS), all measured from the date of randomization. Exploratory objectives aimed at evaluating the impact of PEPI score and residual cancer burden (RCB) on survival outcomes in both arms. Results 53 pts were randomized in each arm (both with 11% Luminal A N+ and 89% Luminal B). 23 of the 53 pts in the LETPAL arm received postoperative adjuvant chemotherapy. Median follow-up is 40.4 months [0-56.6]. 11 progressions have been observed (10 metastatic events, 1 regional progression), of which 3 were in the LETPAL and 8 in the control arm. Two additional iDFS events were observed in the LETPAL arm (secondary malignancies). PFS (HR = 1.01; 95%CI [0.36; 2.90], p=0.98) and iDFS (HR= 0.83; 95%CI [0.31; 2.23], p=0.71) did not differ between both arms. 40 months PFS rate is 86.7% (78.0-96.4) and 87.2% (78.1-97.4) in LETPAL and CT arms respectively. PEPI (PEPI II/II vs I: HR 0.80, 95%CI 0.18-3.67) and RCB scores (RCB II/III vs 0/I: HR 1.36; 95%CI 0.17-10.6) did not appear as independent predictors of PFS or iDFS. Conclusions Despite its small size, NeoPAL suggests that a neoadjuvant LETPAL strategy, together with selected postoperative administration of chemotherapy, may spare chemotherapy in some pts with luminal breast cancer while allowing very good long-term outcomes. Citation Format: Suzette Delaloge, Sylvain Dureau, Véronique D'Hondt, Isabelle Desmoulins, Pierre-Etienne Heudel, François Duhoux, Christelle Levy, Florence Lerebours, Marie Ange Mouret-Reynier, Florence Dalenc, Jean-Sébastien Frenel, Christelle Jouannaud, Laurence Venat-Bouvet, Suzanne Nguyen, Cécile Callens, David Gentien, Jerome Lemonnier, Anne Vincent-Salomon, Hélène Manduzio, Paul-Henri Cottu. Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment in luminal breast cancer: Survival results of the UNICANCER-NeoPAL study [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 PS12-03.

Abstract PS11-08: Operational standardization and quality assurance yield high acceptance rate for breast MRI in the I-SPY 2 TRIAL

Abstract Background: The I-SPY 2 TRIAL is a multi-site response adaptive clinical trial evaluating novel drug combinations for neoadjuvant treatment of breast cancer. Patients receive four or more MRI studies during treatment, and serial measurement of functional tumor volume (FTV) is used to assess response. Under FDA IDE approval, FTV plays an integral role in adjusting patient randomization and evaluating treatment efficacy. FTV is a quantitative measure that requires stringent standards for image quality and protocol adherence. The I-SPY 2 TRIAL consistently reports a high level of data quality and data acceptance for FTV measurements. We present an overview of MRI operational performance and share lessons learned about maintaining high quality MRI data in a multi-site clinical trial. Methods: Over the 10-year course of the I-SPY 2 TRIAL, workflow has been improved to optimize communication between the Imaging Core Lab (ICL) and sites and to collect details about the MRI that are needed for accurate FTV measurement. A standardized imaging acquisition protocol is distributed to all sites, and new sites submit two test cases for review at site initiation. A scan verification form is required for each MRI study completed at sites to document critical information. Sites submit studies using TRIAD image transfer and de-identification software (American College of Radiology), and data is archived and processed at the ICL. All MRI studies are reviewed by the ICL for protocol adherence as soon as they are submitted, and feedback is provided to sites. Image quality factors including motion, fat suppression, and signal-to-noise ratio are qualitatively assessed. The ICL communicates with sites through a centralized email account, regular Coordinator Calls, and Imaging Working Group meetings to discuss emerging issues and offer ongoing training. The ICL contributes to revisions of study protocols and standard operating procedures. Results: As of June 2020, 3020 patients had been registered in I-SPY 2, 1741 patients randomized to treatment with one of 18 experimental drugs or standard therapy (controls), and a total of 7527 MRI studies were performed. FTV could be calculated for 97% (7317/7527) of MRI studies. Of the 7317 studies where FTV could be calculated, relatively minor issues with image quality or imaging protocol adherence were documented for 28% (2030/7317). These issues included motion artifacts (32%, 659/2030), off-protocol scan duration (21%, 433/2030), off-protocol contrast injection rate (14%, 281/2030), and off-protocol imaging field of view (9%, 191/2030). Conclusion: Breast MRI studies using a variety of scan protocols are well-suited for diagnostic evaluation, including BIRADS categorization, measurement of longest diameter, and assessment of lesion washout. The quantitative measures used in the I-SPY 2 trial require adherence to a specific imaging protocol that is kept consistent for all MRI studies for a single patient. Operational standardization, clear communication with sites, and streamlined workflow yield high quality MRI data across multiple sites and scanners. As a result, FTV is a robust biomarker of response to treatment, and is being used to predict patient response and guide treatment planning. We are actively investigating strategies that will improve FTV accuracy for predicting response and informing guidelines for treatment de-escalation. This will allow the ICL to further standardize and improve image quality and will provide the foundation for testing a variety of imaging biomarkers in the I-SPY 2 TRIAL. Citation Format: Jessica Gibbs, David C Newitt, Margarita Watkins, Wen Li, Lisa Cimino, Clifton Li, Natsuko Onishi, Lisa J Wilmes, Teffany Joy Bareng, Evelyn Proctor, Barbara LeStage, Bev Parker, the I-SPY 2 Coodinators, the I-SPY 2 Imaging Working Group, Nola M Hylton. Operational standardization and quality assurance yield high acceptance rate for breast MRI in the I-SPY 2 TRIAL [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 PS11-08.

Abstract PS13-14: A randomized, opened, phase II trial assessing the efficacy and safety of ATH-TH(doxorubicin/docetaxel/trastuzumab followed by docetaxel/trastuzumab) versus TCH(docetaxel/carboplatin/trastuzumab) as neoadjuvant treatment in HER2-positive breast cancer

Abstract Background: Because Pertuzumab hasn't been approved in China until 2020y, trastuzumab has been standard neoadjuvant treatment for HER2-positive breast cancer. But we don't know which is the optimal chemotherapy with or without anthracyclines in the trastuzumab-based HER2-blockade. We designed this clinical trial to compare efficacy and safety between anthracycline and carboplatin in combination with docetaxel and trastuzumab as neoadjuvant therapy. Methods: From Apr, 2013 to Apr, 2019, 124 patients were enrolled. 60 patients were randomly assigned to the ATH-TH group and 64 to the TCH group. The treatment plan is showed as following, 1. TCH group: Trastuzumab(8mg/kg loading dose followed by 6mg/kg maintenance dose on day 1 every 3 weeks) combined with carboplatin(AUC=6 on day1 every 3 weeks) and docetaxel (75mg/m2 d1 every 3 weeks), total 6 cycles ; 2. ATH-TH group: Trastuzumab combined with doxorubicin( 50mg/m2 on day1 every 3 weeks) and docetaxel (75mg/m2 d1 every 3 weeks) after 4 cycles, followed by Trastuzumab plus docetaxel (75mg/m2 d1 every 3 weeks) 4 cycles. Primary endpoint was pCR(ypT0/is/ypN0). Second endpoints included safety, event-free and overall survial (EFS and OS). This trial is registered with ClinicalTrials.gov, number NCT 02510781.Results: Baseline Patients’ characteristics were well balanced between ATH-TH group and TCH group: median age 49y/48y, hormone receptor positive 51.7% vs 46.9%, II stage 60.0% VS 64.0%, III stage 33.3% VS 32.8%. The pCR rate was no significant difference(P=0.457) in ATH-TH 56.7%(95% CI:43.8%-69.6% ) and TCH group 50.0% ( 95% CI :37.4%-62.6%) .In hormone positive subgroup, the pCR rate was 36.7% ( 95% CI:18.4%-55.0% )for TCH group, and 51.6% (95% CI:33.0%-70.2%) for ATH-TH group (P=0.24). In hormone negative subgroup, the pCR rate was 61.8% (95% CI:44.6%-79.0% )for TCH group, and 62.1% ( 95% CI:43.3%-80.9%) for ATH-TH group (P=0.98). The most common adverse events were hematologic toxicities. ATH-TH group had higher 3/4 grade leukocyte decrease rates than TCH group ( 86.7% VS 43.8%, p&amp;lt;0.001) and higher 3/4 thrombocytopenia (11.7% VS 1.6%, p&amp;lt;0.016). ATH-TH group had more FN than (43.3% VS 3.1%, p&amp;lt;0.001). LVEF change and cardiac events were similar between two group Four-year EFS estimates were 94.5% for ATH-TH and 91.1% for TCH (p=0.768, HR=0.82, 95% CI: 0.22-3.06). Four-year OS estimates were 97.5% for ATH-TH and97.8%for TCH (p=0.562, HR=2.0, 95% CI: 0.18-22.2). Conclusions: This is the first prospective randomised trial compare neoadjuvant therapy regimen ATH-TH with TCH in HER2-positive breast cancer. We acquired similar pCR rate, four-year EFS and OS but less toxicity in TCH group compared with ATH-TH. Long-term follow-up is required to confirm these results. Clinical trial information: NCT 02510781. Research Sponsor: None Citation Format: Tao Wang, Jin-Mei Zhou, Xiao-Peng Hao, Hui-Qaing Zhang, Shao-Hua Zhang, Li Bian, Ze-Fei Jiang. A randomized, opened, phase II trial assessing the efficacy and safety of ATH-TH(doxorubicin/docetaxel/trastuzumab followed by docetaxel/trastuzumab) versus TCH(docetaxel/carboplatin/trastuzumab) as neoadjuvant treatment in HER2-positive breast cancer [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 PS13-14.