pCR Rate In Breast Research Articles

Tumor-infiltrating lymphocytes as a predictor of axillary and primary tumor pathological response after neoadjuvant chemotherapy in patients with breast cancer: a retrospective cohort study

PurposeTumor-infiltrating lymphocytes (TILs) can predict complete pathological response (pCR) of tumor in the breast but not so well-defined in the axilla after neoadjuvant chemotherapy. Since axillary surgery is being increasingly de-escalated after NACT, we aimed to investigate the relationship between TILs and pCR in the axilla and breast, as well as survival amongst NACT patients.MethodsClinicopathological data on patients who underwent NACT between 2013 and 2020 were retrospectively examined. Specifically, pre-TILs (before NACT), post-TILs (after NACT) and ΔTIL (changes in TILs) were assessed. Primary endpoint was pCR and secondary endpoints were breast cancer-free interval (BCFI) and overall survival (OS).ResultsTwo hundred and twenty patients with nodal metastases were included. Overall axillary and breast pCR rates were 42.7% (94/220) and 39.1% (86/220), respectively, whereas the combined pCR rate was 32.7% (72/220). High pre-TILs (OR 2.03, 95% CI 1.02–4.05; p = 0.04) predicted axillary pCR whereas, high post-TILs (OR 0.33, 95% CI 0.14–0.76; p = 0.009) and increased ΔTILs (OR 0.25, 95% CI 0.08–0.79; p = 0.02) predicted non-axillary pCR. TILs were not a significant predictor for BCFI and OS.ConclusionsThis study supports the potential use of pre-TILs to select initially node-positive patients for axillary surgical de-escalation after NACT.

Abstract PO2-19-03: Phase 2 study of response-guided neoadjuvant sacituzumab govitecan in patients with localized breast cancer (NeoSTAR)

Abstract Background: Optimizing treatments for localized breast cancer is key to preventing metastatic recurrences and reducing mortality. Sacituzumab Govitecan (SG) is a novel antibody-drug conjugate in which the topoisomerase 1 inhibitor SN-38 (the active metabolite of irinotecan) is coupled to a humanized monoclonal antibody targeting the antigen Trop-2, which is highly expressed in triple negative breast cancer (TNBC). SG is FDA approved for patients with metastatic hormone receptor-positive (HR+) and TNBC. However, efficacy in localized BC is not known. The NeoSTAR clinical trial is evaluating SG in the neoadjuvant (NA) setting for participants with localized breast cancer. Cohort A1 evaluating NA SG monotherapy in localized TNBC is completed, and now cohorts A2 (SG + pembrolizumab (P) for TNBC), B1 (SG monotherapy for HR+ BC), and C (SG + P for HER2- inflammatory breast cancer (IBC)) are enrolling. Trial design: This is a single-arm phase II study of NA SG or SG + P with multiple cohorts across different breast cancer subtypes. In all cohorts, SG is administered via an IV infusion on days 1 and 8 of each 21-day cycle at a starting dose of 10 mg/kg for 4 cycles. For cohorts A2 and C, pembrolizumab is given on day 1 of each cycle. For A2 and B1, after 4 cycles, participants who have biopsy-proven residual disease will have the option to receive additional standard NA therapy at the discretion of the treating physician and subsequently proceed to surgery. Those with a complete response on imaging may proceed directly to surgery. If pathological complete response (pCR) is achieved after 4 cycles of SG + P, participants on A2 will remain on study and receive adjuvant weekly paclitaxel and carboplatin for 12 weeks along with continuation of P to complete a total of one year of the PD-1 inhibitor; participants on B1 will receive adjuvant therapy at the discretion of the treating physician, with the option to continue P to complete a total of one year. On cohort C, after 4 cycles of SG + P, dose-dense doxorubicin + cyclophosphamide + P for 4 cycles will be given before considering surgery. A baseline research biopsy is required for all cohorts, as well as tissue collection following treatment with SG (either at surgery or via biopsy prior to additional NA therapy). Eligibility criteria: Participants ≥ 18 years of age with previously untreated localized breast cancer as determined by the local institution will be enrolled. For A2, participants must either have a primary tumor >2 cm or be node positive. For B1, participants with anatomic clinical stage II-III breast cancer with primary tumor > 1.5 cm and high genomic risk are eligible. For the IBC cohort (C), participants with T4d and any N are eligible. An ECOG performance score of 0 or 1, and adequate bone marrow, hepatic, and renal function is required. Study Objectives: The primary objective is to assess the pCR rate in breast and lymph nodes (ypT0/isN0) with SG + P (A2), SG (B1), or SG + P followed by AC + P (C). Secondary objectives include assessment of overall response rate, evaluation of the safety and tolerability of SG or SG + P (CTCAE v5.0), event-free survival (EFS), and quality of life (EORTC QLQ-C30). Exploratory objectives include assessment of potential predictive biomarkers, including Trop-2 expression, DNA damage response markers and immunological markers, as well as changes in cell free DNA with SG. Statistical methods: The primary analysis is based on the estimated pCR rate with SG or SG + P and will be provided as a proportion (with two-sided 95% confidence interval). Each cohort will follow a Simon two-stage design. EFS will be analyzed using Kaplan-Meier methods and descriptive statistics. Target Accrual: 50 participants (A2), 56 participants (B1), 39 participants (C) Contact: Dr. Laura Spring (LSpring@mgh.harvard.edu) Clinicaltrials.gov #: NCT04230109 Citation Format: Laura Spring, Ana Garrido-Castro, Filipa Lynce, Nadine Tung, Rachel Abelman, Lianne Ryan, Megan Moran, Elizabeth Mittendorf, Leif Ellisen, Sara Tolaney, Aditya Bardia. Phase 2 study of response-guided neoadjuvant sacituzumab govitecan in patients with localized breast cancer (NeoSTAR) [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 PO2-19-03.

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 PO2-03-05: Neoadjuvant anthracycline followed by Toripalimab combined with nab-paclitaxel in patients with stage IIA-IIIC triple negative breast cancer (NeoTENNIS): efficacy and safety results of a phase II study

Abstract Background: Immune checkpoint inhibitors(ICIs)have shown promising antitumor activity in triple negative breast cancer (TNBC) patients. Toripalimab, a novel PD-1 antibody, has been approved for the treatment in multiple solid tumors. However, the neoadjuvant use of toripalimab with chemotherapy has not been evaluated in TNBC patients. In addition, whether chemotherapy could sensitize the ICI treatment has not drawn conclusion yet. In this phase II trial, a sequential use of chemotherapy and anti-PD1 therapy was given in a neoadjuvant setting. The efficacy and safety of toripalimab were evaluated. Patients and methods: Female patients with histologically confirmed stage IIA to IIIC TNBC were included. Eligible patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was pathologic complete response (tpCR; ypT0/is ypN0) rate. Key secondary endpoints were breast pCR (bpCR; ypT0/is) rate, biomarker analysis, and safety. Results: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 patients completed study treatment without progression and received surgery after study treatment. Overall, the percentages of patients with a tpCR and bpCR were 55.7% (39 of 70 patients) and 58.6 % (41 of 70 patients), respectively. For women with CD8–positive and negative tumors, the tpCR rates were 66.0% and 30.0% (P = 0.006), respectively. Significant upregulation of CD8 positive cells after 4 cycles of epirubicin-cyclophosphamide induction chemotherapy (P = 0.011) were shown in sequential biopsy samples. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 30 patients (42.9%), the most common of which were neutropenia (15.7%), leukopenia (14.3%) and alanine aminotransferase increase (4.3%). Most common immune-related AEs were hepatobiliary disorders (Grade 3, 7.2%), creatinine increase (all Grade 1-2, 2.8%) and hypothyroidism (all Grade 1-2, 2.8%). Conclusions: The addition of toripalimab to neoadjuvant chemotherapy is efficacious and safe in patients with locally advanced TNBC. Anthracycline-based chemotherapy could sensitize the ICI treatment with upregulated tumor immune response. The event-free survival results are expected with further follow up. Mechanisms of chemotherapy sensitization are still under investigation (ClinicalTrials.gov number: NCT04418154). Citation Format: Min He, Linxiaoxi Ma, Shuang Hao, Benlong Yang, Bingqiu Xiu, Ya-Yun Chi, Ruo-Hong Shui, Zhong-Hua Wang, Zhi-Ming Shao, Jiong Wu. Neoadjuvant anthracycline followed by Toripalimab combined with nab-paclitaxel in patients with stage IIA-IIIC triple negative breast cancer (NeoTENNIS): efficacy and safety results of a phase II study [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 PO2-03-05.

Real-World Data on Pathological Response and Survival Outcomes After Neoadjuvant Chemotherapy in HER2-Low Breast Cancer Patients

BackgroundData on the pathological responses and survival outcomes after neoadjuvant chemotherapy (NACT) in human epidermal growth factor receptor-2 (HER2)-low breast cancer (BC) are lacking. This study aims to investigate this topic in the real world. MethodsClinicopathological data from 819 HER2-negative BC patients who underwent NACT between 2010 and 2020 were retrospectively retrieved from the Shanghai Jiaotong University Breast Cancer Database. These patients were categorized into HER2-low and HER2-0 groups. Logistic analyses were conducted to identify predictors of complete pathological response (pCR) and breast pCR. Cox regression analyses were conducted to assess the factors associated with disease-free survival (DFS) and overall survival (OS). Kaplan-Meier (K-M) curves were generated to compare DFS and OS between HER2-low BC and HER2-0 BC. ResultsOf the 819 BC patients, 669 (81.7%) had HER2-low tumors, and 150 (18.3%) had HER2-0 tumors. HER2-low BC had a significantly higher ratio of ER ≥ 10%, PR ≥ 20%, and Ki67 ≥ 15% than HER2-0 BC. A significantly higher breast pCR rate was observed in HER2-low BC than in HER2-0 BC (13.6% and 7.3%, respectively, P = .036). Age, HER2 status (low or 0), Ki67, and surgery options were associated with breast pCR in HER2-negative BC. In HER2-low BC, the pCR rate of ER ≥ 10% BC was significantly lower than that of ER < 10% BC, but the DFS and OS of ER 10% BC were significantly higher. The K-M curve showed no significant differences in DFS or OS between HER2-low and HER2-0 BC. Cox regression revealed that ER expression and histological grade (III vs. I∼II) were significantly associated with survival in HER2-low BC. ConclusionsIn this real-world data (RWD) study, a significantly higher breast pCR rate was found in HER2-low BC than in HER2-0 BC, although there was no significant difference in survival. Moreover, ER expression had a significant prognostic impact on HER2-low BC.

Short-term efficacy and safety of neoadjuvant pyrotinib plus taxanes for early HER2-positive breast cancer: a single-arm exploratory phase II trial.

The effectiveness and safety of pyrotinib have been substantiated in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (BC). However, the role of pyrotinib as a single HER2 blockade in neoadjuvant setting among BC patients has not been studied. The objective of this study was to evaluate the efficacy and tolerability of pyrotinib plus taxanes as a novel neoadjuvant regimen in patients with HER2-positive early or locally advanced BC. In this single-arm exploratory phase II trial, patients with treatment-naïve HER2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily and taxanes [docetaxel 75 mg/m2 or nanoparticle albumin-bound (nab)-paclitaxel 260 mg/m2 every 3 weeks, or paclitaxel 80 mg/m2 weekly] for a total of four 21-day cycles before surgery. Efficacy assessment was based on pathological and clinical measurements. The primary endpoint of this study was the total pathological complete response (tpCR) rate. The secondary endpoints included breast pCR (bpCR) rate, investigator-assessed objective response rate (ORR) and adverse events (AEs) profiles. From 1 September 2021 to 30 December 2022, a total of 31 patients were enrolled. One patient was withdrawn due to unbearable skin rash after the second cycle of neoadjuvant therapy. The majority of the intention-to-treat (ITT) population was premenopausal (54.8%), had large tumors (90.3%) and metastatic nodes (58.1%) at diagnosis and hormone-receptor positive tumors (64.5%). Most participants used nab-paclitaxel (74.2%) and received mastectomy (67.7%) after neoadjuvant treatment. The tpCR and bpCR rates were 48.4% [95% confidence interval (CI): 30.8-66%] and 51.6% (95% CI: 34-69.2%), respectively. Grade ≥3 treatment-related AEs were observed in 16.1% (5/31) of the ITT population, including diarrhea (n=2, 6.5%), hand and foot numbness (n=1, 3.2%), loss of appetite (n=1, 3.2%), and skin rash (n=1, 3.2%). AE related dose reduction or pyrotinib interruption was not required. In female patients with HER2-positive non-metastatic BC, neoadjuvant pyrotinib monotherapy plus taxanes appears to show promising clinical benefit and controllable AEs [Chinese Clinical Trial Registry (ChiCTR2100050870)]. The long-term efficacy and safety of this regime warrant further verification.

Real-world data on neoadjuvant chemotherapy with dual-anti HER2 therapy in HER2 positive breast cancer

BackgroundNeoadjuvant chemotherapy with dual-targeted therapy is the standard treatment for human epidermal growth factor 2 (HER2)-positive breast cancer. Although the dual-targeted therapy has significantly improved the pathological complete response (pCR) rate, further investigation is needed to identify biomarkers that predict the response to neoadjuvant therapy.MethodsThis retrospective study analyzed 353 patients with HER2-positive breast invasive ductal carcinoma. The correlation between clinicopathological factors and pCR rate was evaluated. A nomogram was constructed based on the results of the multivariate logistic regression analysis to predict the probability of pCR.ResultsThe breast pCR (b-pCR) rate was 56.1% (198/353) and the total pCR (t-pCR) rate was 52.7% (186/353). Multivariate analysis identified ER status, PR status, HER2 status, Ki-67 index, and neoadjuvant chemotherapy regimens as independent indicators for both b-pCR and t-pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI: 0.68–0.78). According to the nomogram, the t- pCR rate was highest in the ER-PR- HER2-positive patients (131/208) and lowest in the ER + PR + HER2-positive patients (19/73). The subgroup analyses showed that there was no significant difference in pCR rate among the neoadjuvant chemotherapy regimens in ER positive, PR positive, HER2 IHC 2 + , Ki67 index < 30% population. However, for ER-PR-HER2-positive patients, the neoadjuvant chemotherapy regimen has a great influence on the pCR rates.ConclusionsPatients with ER-negative, PR-negative, HER2 3 + and high KI-67 index were more likely to achieve pCR. THP may be used as an alternative to AC-THP or TCbHP in selected HER2-positive patients.

Elasticity Values as a Predictive Modality for Response to Neoadjuvant Chemotherapy in Breast Cancer.

Shear-wave elastography (SWE) is an effective tool in discriminating malignant lesions of breast and axillary lymph node metastasis in patients with breast cancer. However, the association between the baseline elasticity value of breast cancer and the treatment response of neoadjuvant chemotherapy is yet to be elucidated. Baseline SWE measured mean stiffness (E-mean) and maximum stiffness (E-max) in 830 patients who underwent neoadjuvant chemotherapy and surgery from January 2012 to December 2022. Association of elasticity values with breast pCR (defined as ypTis/T0), pCR (defined as ypTis/T0, N0), and tumor-infiltrating lymphocytes (TILs) was analyzed. Of 830 patients, 356 (42.9%) achieved breast pCR, and 324 (39.0%) achieved pCR. The patients with low elasticity values had higher breast pCR and pCR rates than those with high elasticity values. A low E-mean (adjusted odds ratio (OR): 0.620; 95% confidence interval (CI): 0.437 to 0.878; p = 0.007) and low E-max (adjusted OR: 0.701; 95% CI: 0.494 to 0.996; p = 0.047) were independent predictive factors for breast pCR. Low elasticity values were significantly correlated with high TILs. Pretreatment elasticity values measured using SWE were significantly associated with treatment response and inversely correlated with TILs, particularly in HR+HER2- breast cancer and TNBC.

Response-guided neoadjuvant sacituzumab govitecan for localized triple-negative breast cancer: results from the NeoSTAR trial

Sacituzumab govitecan (SG), a novel antibody-drug conjugate (ADC) targeting TROP2, is approved for pre-treated metastatic triple-negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results. Participants with early-stage TNBC received NA SG for four cycles. The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) to SG. Secondary objectives included overall response rate (ORR), safety, event-free survival (EFS), and predictive biomarkers. A response-guided approach was utilized, and subsequent systemic therapy decisions were at the discretion of the treating physician. From July 2020 to August 2021, 50 participants were enrolled (median age= 48.5 years; 13 clinical stage I disease, 26 stage II, 11 stage III). Forty-nine (98%) completed four cycles of SG. Overall, the pCR rate with SG alone was 30% [n= 15, 95% confidence interval (CI) 18% to 45%]. The ORR per RECIST V1.1 after SG alone was 64% (n= 32/50, 95% CI 77% to 98%). Higher Ki-67 and tumor-infiltrating lymphocytes (TILs) were predictive of pCR to SG (P= 0.007 for Ki-67 and 0.002 for TILs), while baseline TROP2 expression was not (P= 0.440). Common adverse events were nausea (82%), fatigue (76%), alopecia (76%), neutropenia (44%), and rash (48%). With a median follow-up time of 18.9 months (95% CI 16.3-21.9 months), the 2-year EFS for all participants was 95%. Among participants with a pCR with SG (n= 15), the 2-year EFS was 100%. In the first NA trial with an ADC in localized TNBC, SG demonstrated single-agent efficacy and feasibility of response-guided escalation/de-escalation. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed.

Efficacy comparisons of solvent-based paclitaxel, liposomal paclitaxel, nanoparticle albumin-bound paclitaxel, and docetaxel after neoadjuvant systemic treatment in breast cancer

PurposeThere are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer. MethodsPatients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion. ResultsThe choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate. ConclusionNab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer.

142P The predictive value of progesterone receptor expression on pCR following neoadjuvant chemotherapy in breast cancer

The efficacy of neoadjuvant chemotherapy (NAC), as measured by the pathological complete response (pCR), varies between molecular subtypes in breast cancer (BC). Oestrogen receptor (ER)-positive, human epidermal growth factor 2 receptor (HER2)-negative patients tend to have lower pCR rates. The transcription of the progesterone receptor (PR) is dependent on the ER therefore PR negativity may suggest an erroneous oestrogen signalling pathway rendering resistance to endocrine therapy. PR- tumours tend to be more aggressive but more chemosensitive. This study aimed to determine if PR status, no longer routinely tested in ER+ BC in the UK, can identify which ER+/HER2- patients will achieve pCR. This would enable more appropriate selection of patients for NAC. Patients undergoing NAC at the Royal Victoria Infirmary, Newcastle, between 2013 and 2021 were identified and their clinicopathological features were collated in a retrospective dataset. PR status was ascertained with standard immunohistochemistry. The PR score was correlated with the pCR rate. Overall survival (OS) and disease-free survival (DFS) were calculated against pCR. 244 patients were included in the analysis (78 triple-negative BC (TNBC); 25 ER+/HER2-; 141 HER2+). In the ER+/HER2- group, PR- patients achieved higher rates of pCR compared to PR+ patients (31% and 9%; χ2; p=0.327). The pCR rate in the ER+/HER2-/PR- group was not statistically different to that of TNBC (31% and 29%; Fisher’s exact test; p=1.000). In the ER+/HER2+ group, PR- patients achieved higher rates of pCR than PR+ patients (23% and 4%; χ2; p=0.090). The breast pCR rate in the ER+/HER2+ group was statistically different (52% and 24%; χ2; p = 0.015) when comparing PR- and PR+ patients. Oncological outcomes of patients that achieved pCR were significantly improved (DFS p = 0.005; OS p = 0.032). PR- patients achieved higher rates of pCR in both ER+/HER2- and ER+/HER2+ subtypes. ER+/HER2-/PR- tumours may behave more like TNBCs than hormone-positive BCs and require more aggressive chemotherapeutic strategies. PR status has value in determining which ER+ patients might benefit from NAC with improved oncological outcomes.

Axillary response and outcome in breast cancer patients after neoadjuvant treatment: The role of radiotherapy in reducing recurrence in ypN0 patients with initially cN+ stage.

We aim to explore the clinicopathological features associated with axillary node response and recurrence in breast cancer patients undergoing neoadjuvant treatment (NAT). We retrospectively reviewed the medical records of 486 stage I to III breast cancer patients who received NAT and surgery between 2016 and 2021. A total of 486 cases were reviewed and 154 (31.7%) patients achieved breast pathological complete response (pCR) (ypT0/Tis). Of the 366 cases with initially cN+, 177 (48.4%) cases reach ypN0. Breast pCR is in high accordance to axillary pCR (81.5%). Hormone receptor (HR)-/HER2+ breast cancer patients have the highest axillary pCR rate (78.3%). Patients achieve axillary pCR have a significantly better disease-free survival (DFS) (P=0.0004). Further analysis reveals that the DFS of ypN0 and ypN1 cases are similar (P=0.9049). Moreover, DFS in patients with ypN0 (P<0.0001) and ypN1 (P<0.0001) is significantly better than that in patients with ypN2-3. For post-mastectomy ypN0 cases, radiation could only improve DFS in patients with initially cN+ stage (P=0.0499). Multivariate Cox regression analysis shows that radiation is an independent factor to improve DFS (Hazard ratio (HR): 0.288(0.098-0.841), P=0.0230). Radiation does not improve DFS in pre-cN0/ypN0 patients (P=0.1696). Axillary pCR rate is higher than breast pCR rate. HR-/HER2+ patients have the highest axillary pCR rate. Axillary pCR is associated with better DFS. Radiation could further improve DFS in ypN0 patients with initially positive nodal disease.

Abstract P3-07-07: The use of ribociclib/letrozole combination as an alternative for neoadjuvant chemotherapy in selected patients with early luminal breast cancer

Abstract Introduction In hormone receptor-positive, HER2-negative early-stage breast cancer (BC), cyclin-dependent kinases 4 and 6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) could represent an alternative to neoadjuvant chemotherapy (NAC). Methods NEOLBC is a randomized phase II trial that tailored neoadjuvant therapy in postmenopausal patients with early, luminal (ER &amp;gt;50%, PR any), HER2-negative, stage II/III BC based on the percentage of Ki67 positive cancer cells after a window of opportunity of two weeks letrozole. Patients with a Ki67 &amp;gt;= 1% after 2 weeks were randomized between ribociclib plus letrozole (RL) and chemotherapy (CT; AC-T regimen). The primary objective was to determine if RL gives a doubling in complete cell cycle arrest (CCCA; Ki67 &amp;lt; 1% on IHC) as compared to CT in the surgical specimen (70% vs. 35% of patients, respectively). Secondary endpoints included pathological response, toxicity and ER pathway activity (measured by the OncoSIGNal qPCR test). Results Out of 161 registered patients, 70 patients were randomized and 66 patients started treatment; 34 RL and 32 CT. Patient characteristics were equally distributed between the two groups, except for the PR status (RL 23.5% negative vs. 50.0% negative in the CT group). In the intention to treat analysis, the CCCA in the surgical specimen was similar for both groups: 35.3% in the RL vs. 31.3% in the CT group (p = 0.73). The pathological complete response (pCR) in the breast was not significantly different between the two groups (11.8% vs. 3.1%, p = 0.36) nor was the pCR rate in breast plus lymph nodes (8.8% vs. 3.1%, p = 0.61) for the RL vs. CT group, respectively. An explorative analysis on the difference in Ki67% (decline, no change, increase) from baseline to surgery showed a decline in 73.5% vs. 50.0%, no change in 17.6% vs. 31.3% and an increase in 8.8% vs. 18.8% of patients (p = 0.06) for the RL vs. CT group, respectively. In the RL group eight patients (23.5%) discontinued ribociclib early due to toxicity (two SAE’s were observed) vs. 10 patients (31.3%) discontinuing treatment in the CT group (one SAE was observed). Secondary endpoints, including the ER pathway activity analysis, will be presented in-depth during the meeting. Conclusion Although the primary endpoint was not met, the NEOLBC trial showed a similar CCCA and pathological response at surgery for RL vs. CT. Therefore, RL as an alternative for NAC merits further investigation in follow-up studies. ClinicalTrials.gov: NCT03283384 Citation Format: Anne Florine de Groot, Danielle Cohen, Joan B. Heijns, Caroline Mandigers, Diederick M. Keizer, Hein Putter, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Kyra Dijkstra, Elise van Leeuwen-Stok, Gerrit-Jan Liefers, Sabine Linn, Judith Kroep. The use of ribociclib/letrozole combination as an alternative for neoadjuvant chemotherapy in selected patients with early luminal breast cancer [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 P3-07-07.

Abstract PD16-03: Use of post-neoadjuvant chemotherapy image-guided breast vacuum assisted biopsy to predict residual cancer in exceptional responders: A prospective cohort study

Abstract Background: Post-neoadjuvant chemotherapy (NAC) image-guided biopsy of the residual imaging abnormality/tumor bed is increasingly used to assess residual disease in the breast and potentially identify exceptional responders who may not require surgical intervention. Previous studies have shown variable results on the diagnostic performance of this technique. The aim of this analysis was to assess the accuracy of post-NAC, image-guided vacuum assisted biopsy (VAB) to predict residual disease in the breast using a standardized assessment protocol. The findings could help further support the optimal design of trials omitting surgery in selected patients. Methods: Prospective cohort study (BR154b) of consecutive patients with HER2 positive and triple negative (TN) invasive ductal carcinoma (IDC), treated with NAC, who underwent post-NAC VAB to aid surgical planning between 02/2018 and 06/2022 at one institution. Patients with complete/near complete imaging response (residual imaging abnormality ≤ 2cm) had a VAB to sample ≥ 90% of the breast residuum/tumor bed previously marked by clip insertion. Biopsy samples were defined as representative if pathology features suggestive of tumor bed or residual cancer were identified. Pathologic complete response (pCR) was defined as no residual invasive or in situ disease in the breast (ypT0). Diagnostic accuracy of VAB was calculated using final surgical pathology as the reference standard. Simple descriptive statistics were used. Results: A total of 54 women met the eligibility criteria and underwent post-NAC VAB. This was not representative in 3 cases and therefore 51 women were included in the analysis. Median age was 49 years [interquartile range (IQR): 43 – 61]. The majority of cancers were grade 3 (n=31) or grade 2 (n=19). Subtype distribution was 21 (41.2%) for hormone receptor (HR) positive/HER2 positive, 13 (25.5%) for HR negative/HER2 positive and 17 (33.3%) for TN IDC. There was associated DCIS at diagnosis in 37.3% of cases. The majority of the cancers at presentation were T2 (n=35, 68.6%) with a median tumor size on imaging of 28 mm (IQR: 28 – 43). There were associated microcalcifications in 29 cases (n=11 extending beyond the main tumor). Sixteen women presented with cN+ disease. On completion of NAC, 19 women had complete imaging response, while in the remaining the median size of the residual imaging abnormality was 12 mm (IQR: 9 – 16). A post-NAC VAB was performed with ultrasound or stereo-guidance in 48 and 3 cases respectively. The median size (gauze) of needle used was 10 (IQR: 10) and the median number of cores obtained was 8 (IQR: 6-8). In the surgical specimen, the overall breast pCR rate was 58.8% (52.4% for HR positive/HER2 positive, 76.9% for HR negative/HER2 positive and 52.9% for TN). The axillary pCR rate was 81.25%. The false negative rate (FNR) of post-NAC VAB was 4.76% (1/51, 95% CI: 0.12 – 23.82%). The sensitivity and specificity for residual disease were 95.24% (95% CI: 76.18 – 99.88) and 93.33% (95% CI: 77.93 – 99.18) respectively. The negative predictive value was 96.55% (95% CI 80.49 – 99.48) and the overall accuracy 94.12% (95% CI: 83.76 – 98.77). Conclusions: This analysis suggests that a standardized assessment protocol using image-guided VAB in patients with HER2 positive or TN IDC and exceptional response to NAC (residual imaging abnormality/tumor bed measuring ≤ 2 cm) aiming to sample ≥ 90% of the breast residuum allows reliable prediction of residual disease and breast pCR with a FNR &amp;lt; 5%. These results further support the optimal design of de-escalation trials in NAC exceptional responders testing the safety of omitting surgery. Citation Format: Marios Konstantinos Tasoulis, Romney Pope, Tanja Gagliardi, Ashutosh Nerurkar, Alicia F. Okines, Nicholas Turner, Fiona MacNeill. Use of post-neoadjuvant chemotherapy image-guided breast vacuum assisted biopsy to predict residual cancer in exceptional responders: A prospective cohort study [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 PD16-03.

Phase 2 study of response-guided neoadjuvant sacituzumab govitecan (IMMU-132) in patients with localized triple-negative breast cancer: Results from the NeoSTAR trial.

512 Background: Sacituzumab govitecan (SG), a novel antibody-drug conjugate in which the topoisomerase 1 inhibitor SN-38 (active metabolite of irinotecan) is linked to a humanized monoclonal antibody targeting the tumor antigen Trop2, is currently approved for treatment of patients (pts) with pre-treated metastatic triple negative breast cancer (TNBC). We conducted a phase 2 study evaluating neoadjuvant (NA) SG as upfront therapy for pts with localized TNBC (NCT04230109). The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) with SG. Secondary objectives included assessment of radiological response rate, evaluation of the safety and tolerability (CTCAE v5.0) and event-free survival (EFS). Methods: Patients with localized TNBC (tumor size ≥1cm, or any size if node positive) with no prior treatment were eligible. SG was administered IV on Days 1, 8 of each 21-day cycle at a starting dose of 10 mg/kg for 4 cycles. After 4 cycles, patients with biopsy-proven residual disease, considered as no pCR for primary endpoint, had the option to receive additional NA therapy at the discretion of the treating physician. Radiologic response (US or MRI) was defined by RECIST version 1.1 using a composite response of CR &amp; PR. Standard descriptive statistics were utilized, including 95% binomial confidence intervals for all rates estimated. Results: From 7/14/20 – 8/31/21, 50 pts were enrolled (median age = 48.5; 11 stage I disease, 24 stage II, 11 stage III, 4 unknown; 62% node negative). The majority (98%; n = 49) of pts completed 4 cycles of SG. Overall, the radiological response rate with SG alone was 62% (n = 31, 95% CI 48%, 77%). 26 pts proceeded directly to surgery after SG. Overall, the pCR rate with SG alone was 30% (n = 15/50, 95% CI 18%, 45%). The other 11 pts had RCB-1 (n = 3), RCB-2 (n = 5), and RCB-3 (n = 3) disease, respectively. Of the 24 pts who received additional NA therapy, 6 had a pCR (3 received anthracycline-based regimen, 2 carboplatin/taxane, and 1 docetaxel/cyclophosphamide). Among pts with a germline BRCA mutation (n = 8), 7 proceeded directly to surgery after SG and 6 had a pCR (86%, 95% CI 42%, 99%). The most common AEs with SG were nausea (82%, n = 41), fatigue (78%, n = 39), alopecia (76%, n = 38), neutropenia (58%, n = 29), anemia (36%, n = 18), and rash (48%, n = 24). 6% of pts required dose-reduction. No pts discontinued SG therapy due to disease progression or AEs; 1 discontinued due to minimal response per investigator preference. At the time of data cut-off (1/18/22), no pts experienced disease recurrence. Updated biomarker and EFS results will be presented at the meeting. Conclusions: In the first neoadjuvant trial in TNBC with an ADC, SG demonstrated single agent efficacy in localized TNBC. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed. Clinical trial information: NCT04230109.

Abstract OT-03-06: Phase 2 study of response-guided neoadjuvant sacituzumab govitecan (IMMU-132) in patients with localized triple-negative breast cancer (NeoSTAR)

Abstract Background: Optimizing treatments for triple negative breast cancer (TNBC) in the localized breast cancer setting is key to preventing metastatic recurrences and reducing mortality from this devastating disease. Sacituzumab Govitecan (SG), a novel antibody-drug conjugate in which the topoisomerase 1 inhibitor SN-38 (the active metabolite of irinotecan) is coupled to a humanized monoclonal antibody targeting the tumor antigen Trop-2, was granted FDA accelerated approval in April 2020 for treatment of patients with metastatic TNBC. The NeoSTAR clinical trial is evaluating SG in the neoadjuvant setting for patients with localized TNBC. Trial design: This is a single arm phase II study of neoadjuvant SG in patients with localized TNBC. SG will be administered via an IV infusion on Days 1, 8 of each 21-day cycle at a starting dose of 10 mg/kg for 4 cycles. After 4 cycles, patients who have biopsy-proven residual disease will have the option to receive additional standard neoadjuvant therapy at the discretion of the treating physician and subsequently proceed to surgery. Those with a complete response on imaging may proceed directly to surgery. A baseline research biopsy prior to initiation of study therapy is required as well as tissue collection following treatment with SG (either at surgery or via biopsy prior to additional neoadjuvant therapy). Eligibility criteria: Patients ≥ 18 years of age with previously untreated primary TNBC as determined by the local institution according to ASCO/CAP criteria will be enrolled. Patients must either have a primary tumor &amp;gt;1 cm measured by imaging (cT1c-T4), or be node positive. An ECOG performance score of 0 or 1, and adequate bone marrow, hepatic, and renal function is required. Specific aims: The primary objective is to assess the pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) with SG. Secondary objectives include assessment of radiological response rate, evaluation of the safety and tolerability of SG (CTCAE v5.0), disease-free survival (DFS), and quality of life (EORTC QLQ-C30). Exploratory objectives include assessment of potential predictive biomarkers, including Trop-2 expression, DNA damage response markers and immunological markers, as well as changes in cell free DNA with SG. Statistical methods: The primary analysis is based on the estimated pCR rate with SG and will be provided as a proportion (with two-sided 95% confidence interval). Accounting for up to a 14% drop out rate, a sample size of 43 patients will provide 80% power to exclude a lower limit of pCR of 20% (alpha 0.05, two-sided test). DFS will be analyzed using Kaplan-Meier methods and descriptive statistics. Target Accrual: 50 patients. Contact: Dr. Laura Spring (LSpring@mgh.harvard.edu) Clinicaltrials.gov #: NCT04230109 Citation Format: Laura M. Spring, Sara M. Tolaney, Neelam Desai, Amy Comander, Therese Mulvey, Ian E. Krop, Eric P. Winer, Elizabeth A. Mittendorf, Leif W. Ellisen, Aditya Bardia. Phase 2 study of response-guided neoadjuvant sacituzumab govitecan (IMMU-132) in patients with localized triple-negative breast cancer (NeoSTAR) [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 OT-03-06.

How Effective is Neoadjuvant Endocrine Therapy (NET) in Downstaging the Axilla and Achieving Breast-Conserving Surgery?

Neoadjuvant endocrine therapy (NET) is effective in downstaging large hormone receptor-positive (HR+) breast cancers and increasing rates of breast-conserving surgery (BCS), but data regarding nodal pathologic complete response (pCR) are sparse. We reported nodal and breast downstaging rates with NET, and compared axillary response rates following NET and neoadjuvant chemotherapy (NAC). Consecutive stage I-III breast cancer patients treated with NET and surgery from January 2009 to December 2019 were identified from a prospectively maintained database. Nodal pCR rates were compared between biopsy-proven node-positive patients treated with NET, and HR+/HER2- patients treated with NAC from November 2013 to July 2019. 127 cancers treated with NET and 338 with NAC were included. NET recipients were older, more likely to have lobular and lower-grade tumors, and higher HR expression. With NET, the nodal pCR rate was 11% (4/38) of biopsy-proven cases, and the breast pCR rate was 1.6% (2/126). Nodal-dowstaging rates with NET and NAC were not significantly different (11% vs 18%; P = 0.37). Patients achieving nodal pCR with NET versus NAC were older (median age 70 vs 50, P = 0.004) and had greater progesterone receptor (PR) expression (85% vs 13%, P = 0.031), respectively. Of patients not candidates for BCS due to a large tumor relative to breast size, 36/47 (77%) became BCS-eligible with NET (median PR expression 55% vs 5% in those remaining ineligible, P < 0.05). Although nodal pCR is more frequent than breast pCR, NET is more likely to de-escalate breast surgery than axillary surgery. However, with a nodal pCR rate of 11%, NET remains an option for downstaging node-positive patients without clear indications for NAC.

Abstract P5-04-10: Immune and transcriptional signatures of dendritic cell (DC) vaccination combined with chemotherapy in locally advanced, triple-negative breast cancer (TNBC) patients

Abstract Women with triple-negative breast cancer (TNBC) have an increased pathologic complete response rate (pCR; residual disease after neoadjuvant chemotherapy) as compared to women with non-TNBC, and those with pCR have a 90% disease-free survival. However, women with TNBC who do not achieve a pCR have an increased risk of recurrence, decreased overall survival, and post-recurrence survival as compared to women with non-TNBC who do not achieve a pCR. A high priority for clinical research is therefore to increase the pCR rate in breast and axilla with preoperative therapy, as therapeutic options for patients who do not have a pCR are limited. Immunotherapy is an attractive strategy as human BCs can be immunogenic and enhancing the immune effector function may augment the cytotoxic effects of standard therapies. Immunity against tumor antigens can be boosted in cancer patients by vaccination with ex vivo-generated tumor antigen-loaded DCs. Here, we report the extended analysis of a clinical trial on 10 TNBC pts assessing the feasibility of combining cyclin B1/WT1/CEF (antigen)-loaded DC vaccination with preoperative chemotherapy in patients with locally advanced TNBC. Combination of preoperative chemotherapy and intratumoral and subcutaneous autologous DC vaccination led to 70% of combined rate of pCR and residual cancer burden 1 (RCB1). To assess expansion of antigen-specific T cell responses, IFN-g-ELISpot was carried out with PBMCs from baseline (BL) and several time points during vaccine treatment that were cultured with control peptides or with peptide libraries covering vaccine antigens. The expansion of antigen-specific immune responses could be detected at various time points post treatment. Transciptional profiling on blood (Nanostring) and tumors (RNAseq) revealed profound changes in immune transcription signatures. T cell and DC signatures in blood and T cell, inflammation, cytotoxic and cell cycle signatures in pre-chemotherapy breast cancer biopsies were linked with pathological responses in definitive surgery specimens. Taken together, differential gene and immunologic signatures of the pre-treatment breast cancer biopsies distinguish pts who have a pCR vs no pCR and can identify potential therapeutic targets for pts with TNBC. Citation Format: Te-Chia Wu, Joyce O’Shaughnessy, Lee K. Roberts, Jennifer L. Smith, Susan B. Burkeholder, Jennifer Finholt, Jessica Tarnowski, Tuoc Dao, Jeffrey Lamont, Sandra M. Zurawski, Phuong Nguyen, Yuanyuan Wang, Kyung In Kim, Derek Blankenship, Jacob Turner, Xuan Wang, Florentina Marches, Maren K. Levin, Michael Grant, Gerard Zurawski, Virginia Pascual, Jacques Banchereau, Karolina Palucka. Immune and transcriptional signatures of dendritic cell (DC) vaccination combined with chemotherapy in locally advanced, triple-negative breast cancer (TNBC) patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-10.

Biological subtype, treatment response and outcomes in inflammatory breast cancer using data from the National Cancer Database.

Although inflammatory breast cancer (IBC) is postulated to be a distinct biological entity, practice guidelines and previous data suggest that treatment and outcomes are influenced by standard approximated biological subtype. The aim of this study was validation in a large recent National Cancer Database (NCDB) patient cohort. Patients with non-metastatic IBC treated in 2010-2015 with neoadjuvant systemic therapy and surgery were identified from the NCDB. Approximated biological subtypes were categorized as oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), ER-/HER2- and HER2+. Total pathological complete response (pCR) was defined as ypT0/ypTis, ypN0. χ2 tests were used to compare pCR rates, and Kaplan-Meier curves and Cox proportional hazards regression to analyse overall survival. Among 4068 patients with IBC (median age 56 years), the approximated biological subtype was ER+/HER2- in 1575 (38·7 per cent), HER2+ in 1323 (32·5 per cent) and ER-/HER2- in 1170 (28·8 per cent). A total of 3351 patients (84·0 per cent) were cN+ at presentation, with no differences across subtypes. Total pCR rates varied significantly by subtype: ER+/HER2- (6·2 per cent), HER2+ (38·8 per cent), ER-/HER2- (19·1 per cent) (P < 0·001), as did breast pCR rates (10·4, 44·5 and 25·2 per cent respectively) and nodal pCR rates (16·9, 56·9 and 33·1 per cent). The 5-year overall survival rate varied significantly across subtypes (ER+/HER2- 64·9 per cent, HER2+ 74·0 per cent, ER-/HER2- 44·0 per cent; P < 0·001) and by pCR within subtypes (all P < 0·001). In multivariable analysis, ER-/HER2- subtype (hazard ratio 2·89 versus HER2+ as reference; P < 0·001) and absence of total pCR (hazard ratio 3·23; P < 0·001) predicted worse survival. Both treatment response and survival in patients with IBC varied with approximated biological subtype, as among other invasive breast cancers. These data support continued tailoring of systemic treatment to approximated biological subtype and highlight the recent improved outcomes in patients with HER2+ disease.

Pegylated liposomal doxorubicin plus cyclophosphamide followed by docetaxel as neoadjuvant chemotherapy in locally advanced breast cancer (registration number: ChiCTR1900023052)

Anthracyclines have a profound effect on breast cancer. However, at higher dosages, there are many toxic side effects associated with their use; these include bone marrow suppression, alopecia, gastrointestinal reactions and cardiotoxicity. Pegylated liposomal doxorubicin (PEG-LG) has been demonstrated to achieve equivalent efficacy to conventional doxorubicin, with significantly lower cardiotoxicity. We conducted an open-label, multicenter, single-armed clinical trial useing an NAC regimen based on four cycles of PEG-LD 40 mg/m2 plus cyclophosphamide (CPM) 600 mg/m2 on day 1 of a 21 day schedule, followed by four cycles of docetaxel (DTX) 85 mg/m2 on day 1 of a 21 day schedule. The primary endpoint analysed was the pathological complete response rate (pCR) in the breast, while treatment toxicities and safety were also assessed. The results showed that the breast pCR rate was 18.75% (95% CI 11.5–26.0%). Among the different molecular cancer types, the triple negative breast cancer patients had the highest pCR, at 43.75%. No significant decrease in left ventricular ejection fraction was observed. Our data tends to draw the conclusion that this regimen is a viable option for the neoadjuvant treatment of patients with LABC, especially in the triple-negative subtype and patients with heart abnormalities. We believe the efficacy and the safety of this regimen is likely to be the same based on published data from other studies but that this cannot be certain without a randomized trial.