Breast Pathologic Complete Response Research Articles

Residual Axillary Metastases in Node-Positive Breast Cancer Patients After Neoadjuvant Treatment: A Register-Based Study.

Lymph node (LN) metastasis after neoadjuvant chemotherapy (NACT) generally warrants axillary lymph node dissection, which opposes guidelines of upfront surgery in many cases. We investigated the risk of having additional metastases in the axilla when the LNs removed by targeted axillary dissection (TAD) harbored metastases after NACT. We aimed to identify subgroups suitable for de-escalated axillary treatment. This register-based study used data from the Danish Breast Cancer Cooperative Group database. Data were analyzed with logistic regression models. The primary outcome was the metastatic burden in non-TAD LNs in patients with positive TAD LNs after NACT. Among 383 patients, < 66.6% positive TAD LNs (adjusted odds ratio [OR] 0.34, 95% confidence interval [CI] 0.17-0.62), only isolated tumor cells (ITCs) [OR 0.11, 95% CI < 0.01-0.82], and breast pathological complete response (pCR) [OR 0.07, 95% CI < 0.01-0.56] were associated with a low risk of having more than three positive non-TAD LNs. In 315 patients with fewer than three positive non-TAD LNs, the proportion of positive TAD LNs (OR 0.45, 95% CI 0.27-0.76 for 33.3-66.6% vs. > 66.6%), size of the TAD LN metastasis (OR 0.14, 95% CI 0.04-0.54 for ITC vs. macrometastasis), tumor size at diagnosis (OR 0.30, 95% CI 0.15-0.64 for 20-49mm vs. ≥ 50mm) and breast pCR (OR 0.38, 95% CI 0.15-0.96) were associated with residual LN metastases in the axilla. Breast pCR or ITC only in TAD LNs can, with reasonable certainty, preclude more than three positive non-TAD LNs. Additionally, patients with only ITCs in the TAD LN had a low risk of having any non-TAD LN metastases after NACT. De-escalated axillary treatment may be considered in both subgroups.

Abstract PO4-19-10: Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy In HER-2 Positive/Triple Negative Breast Cancer Patients With Excellent Radiologic Response to the Breast and Axilla

Abstract Background Neoadjuvant chemotherapy (NACT) for breast cancer (BC) is downstaging inoperable tumors into operable tumors and de-escalating breast/axillary surgery. According to advanced NACT, dual human epidermal growth factor-2 (HER2) blockage in HER2-positive BC, carboplatin, and immunotherapy in triple-negative breast cancer (TNBC) revealed pathologic complete response (ypCR) rates of up to 68% and 80%, the indications for NACT have expanded to early BC and the expected ypCR rate has increased. Therefore, it may be reasonable to consider omitting surgery in cases with excellent responses to NACT. Although sentinel lymph node biopsy (SLNB) is minimally invasive, some patients still experience complications such as lymphedema, pain, sensory loss, and axillary web syndrome. Several recent retrospective studies and pilot prospective studies have reported axillary pathologic complete response (ApCR) is highly correlated with breast pathologic complete response (BpCR). In cN0 with HER2+ BC and TNBC, the ApCR rate in BpCR after NACT was reported up to 100%, and in cN1 with HER2+ BC and TNBC, the ApCR rate in BpCR after NACT was reported about 85%. There are many studies predicting BpCR using radiologic imaging such as breast mammography (MMG), ultrasonography (USG), and magnetic resonance imaging (MRI). However, the combination of tri-modality (MMG, USG, MRI) could not confirm BpCR. The current study is screened in cT1-3N0-1M0, HER2+ or TNBC, and planned breast-conserving surgery (BCS) patients after NACT with excellent response at the combination of tri-modality imaging (breast MMG, breast USG, breast MRI) and with expected BpCR at physical examination. Methods Trial design The ASLAN trial is a prospective, multicenter, single-arm, clinical study. The five tertiary care hospitals in South Korea are participating which are members of the Korean Breast Cancer Study Group (KBCSG). Eligibility Inclusion criteria: women aged 20-69; cT1-3N0-1M0; HER2+ or TNBC (defined by ER-negative (&amp;lt; 10% positive cells in IHC) and PR-negative (&amp;lt; 10% positive cells in IHC)); expected complete remission at physical examination and radiological expected Tumor size ≤ 2cm or non-mass enhancement ≤ 4cm at breast MRI after standard NACT; planned breast-conserving surgery (BCS) with whole-breast irradiation; ECOG performance status 0-1. Exclusion criteria: SLNB before NACT; previous axillary surgery; bilateral BC; pregnancy. Intervention In eligible patients, BCS was performed. After BCS, patients who showed BpCR are enrolled with the omission of SLNB. Patients with no BpCR proceed with routine axillary surgery. Sample size calculation The assumption for an acceptable 5-year RFS ≥84% is based on previous study findings. The calculated total case number for per-protocol analysis is N=178. By Jun 2023, 153 patients had been enrolled and the target accrual of 178 patients is expected to be complete by Dec 2023. Study outcomes Primary endpoint: 5-year recurrence-free survival. Secondary endpoint: local recurrence-free survival, breast cancer-specific survival, overall survival, ipsilateral axillary recurrence interval, distant metastasis-free survival, contralateral breast-free survival, re-operation rate according to breast biopsy after NACT, adverse event, and quality of life. Accrual Plans The first patient was enrolled on Sep 2021. Among 223 patients who were screened, 153 patients have been enrolled in Jun 2023. We plan to complete the target accrual by Dec 2023. Conclusion The primary aim of the ASLAN trial is to demonstrate the oncologic safety of omitting axillary surgery for the excellent response after NACT in HER2+ or TNBC, early breast cancer patients undergoing BCS and adjuvant RT ASLAN trial, altogether with the EUBREAST-01 and ASCIS trials, will answer the very important question that may alter the axillary surgery in highly selected patients after NACT Citation Format: Jai Min Ryu, Wonshik Han, Han-Byoel Lee, Sung Gwe Ahn, Hee Jeong Kim, Hyung Seok Park, Ji Soo Choi, Hyunjun Lee, Hae Young Kim, Jeong Eon Lee. Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy In HER-2 Positive/Triple Negative Breast Cancer Patients With Excellent Radiologic Response to the Breast and Axilla [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 PO4-19-10.

Abstract PO3-25-11: Unprecedented responses to neoadjuvant sequential administration of Tocilizumab followed by cisplatin/docetaxel for locally advanced triple negative breast cancer patients

Abstract Background: Triple negative breast cancer (TNBC) remains a challenge for clinicians due to its aggressive behavior and scarcity of effective treatment. Interleukin 6 (IL-6) is well known to contribute to poor therapeutic gain, tumor relapse and aggressive tumor growth. Here we have explored targeting the IL-6 signaling pathway by Tocilizumab (Actemra) as a new potential therapeutic approach for the treatment of TNBC. Methods: The study population includes thirty (30) patients with (T2-T4, N0-3) stage (IIB-III) TNBC treated uniformly with Tocilizumab followed with cisplatin/docetaxel according to a traditional 3+3 design using a sentinel patient at each cohort. Eligible patients received Tocilizumab on day 1 followed by cisplatin/docetaxel on day 2 every 4 weeks for a total of six cycles. The primary end points were pathological complete response in breast and axilla (pCR) (ypT0/ypN0) and assessment for tolerability/toxicities profiles. Additionally, the status of the BRCA1 and BRCA2 genes was determined in all patients. Results: Eligible patients who were enrolled in this phase I/II trial had a median age of 42 years, with 63% premenopausal and 67% had nodal involvement at base line. The median tumor size was 45 mm (range 25-150 mm), stage III A/B 26% and stage IIIC 50%. Germline BRCA1/2 mutations represented 27%. The overall pCR and (RCB class 0+1) were 66% and 69%, respectively. Interestingly, pCR reached 81% in axilla, and 100% in patients with tumors bearing BRCA1/2 mutations. Interestingly, tocilizumab affected the blood level of several pro-carcinogenic cytokines. Conclusions: To our knowledge this novel therapeutic strategy is the first to report the inhibition of a cytokine signaling (a new class of biological therapy) in combination with chemotherapy for the intricate and hard-to-treat TNBC patients with unprecedented responses and acceptable tolerability/toxicities, which merits further investigation. Pending Patents: US Patent Application No. 18/122,839 European Patent Application No. 23 162 694.6 Citation Format: Taher Al-Tweigeri, Noura Alraouji, Asma Tulbah, Syed Akhtar, Meshari Alzahrani, Saleh Najjar, Dahish Ajarim, Kauser Suleman, Adher Al Sayed, Abdelilah Aboussekhra. Unprecedented responses to neoadjuvant sequential administration of Tocilizumab followed by cisplatin/docetaxel for locally advanced triple negative breast cancer patients [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 PO3-25-11.

Abstract PO5-18-10: Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104)

Abstract Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 48 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (&amp;lt; 10% positive cells in IHC) and PgR-negative (&amp;lt; 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2024 -Primary outcome analysis: Q1/2027 Current accrual: In June 2023, 255 patients were recruited; the majority of them in Germany. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy). Citation Format: Toralf Reimer, Bernd Gerber, Thorsten Kuehn, Nikola Bangemann, Anke Kleine-Tebbe, Andrea Stefek, Ulrike Doerste, Carolin Hammerle, Oliver Hoffmann, Alexander Hein, Isabel Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [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 PO5-18-10.

Abstract GS02-07: Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304

Abstract Background: The benefit of adjuvant regional nodal irradiation including the chest wall after mastectomy (CWI+RNI) and with whole breast irradiation (WBI+RNI) after breast conserving surgery (BCS) is well established in pts with pathologically positive axillary nodes (pN+). Pts who present with axillary node involvement (cN+), receive neoadjuvant chemotherapy (NC), and are found to be pathologically node-negative at surgery (ypN0), have lower loco-regional recurrence (LRR) rates compared to those who remain pathologically node-positive (ypN+). This phase III, randomized trial aimed to evaluate whether CWI+RNI after mastectomy or addition of RNI to WBI after BCS significantly improves invasive breast cancer recurrence-free interval (IBC-RFI) in cN+ pts found to be ypN0 after NC. Methods: Eligible pts had clinical cT1-3, N1, M0 invasive breast cancer (biopsy-proven N+ by FNA/core needle bx), completed ≥8 wks of NC (and anti-HER2 therapy if HER2+), and were ypN0 after mastectomy or BCS and sentinel node biopsy (SLNB, ≥2 nodes), axillary lymph node dissection (ALND), or both. Pts were randomized to “No RNI” (i.e., observation after mastectomy or WBI after BCS) vs. “RNI” (i.e., CWI+RNI after mastectomy or WBI+RNI after BCS). Primary endpoint was IBC-RFI. Secondary endpoints reported here: LRR-free interval (LRRFI), distant recurrence-free interval (DRFI), disease-free survival (DFS), and overall survival (OS). Study was designed to have 80% power to detect 35% reduction in annual rate of IBC-RFI for an absolute risk reduction of 4.6% (5-yr cumulative rate). Per protocol, final analysis was to occur after 172 events or 10 yrs after study initiation.Here we report the time-driven analysis prespecified in the protocol. Results: From 9/13-12/20, 1,641 pts were enrolled; 1,556 pts were available for primary event analysis; median f/u time 59.5 mos (IQR 40.7-74.1). Pt/tumor characteristics were well balanced between groups. Median age 52 yrs (range 21-84); 31% non-white; 21% cT1, 60% cT2, 19% cT3; 23% triple-negative, 21% HR+/HER2-, 56% HER2+; 58% BCS; 55% SLNB, 45% ALND+/-SLNB; and 78% had breast pathologic complete response. At the time of the analysis, 109 IBC-RFI events (63% of the planned 172) were confirmed (“No RNI”: 59, “RNI”: 50). There was no statistically significant difference between groups for IBC-RFI (HR=0.88, 95%CI 0.60-1.29; p=0.51), 5-yr point estimates: 91.8% for “No RNI” and 92.7% for “RNI.” There were no statistically significant differences between the treatment groups for secondary endpoints. There were no study-related deaths and no unexpected toxicities.Grade 4 toxicity was rare (0.1% with “No RNI”, 0.5% with “RNI”); 6.5% of pts developed grade 3 toxicity in “No RNI” and 10% in “RNI” group. Most common grade 3 toxicity was radiation dermatitis (3.3% in “No RNI,” 5.7% in “RNI”). Conclusion: In pts who present with biopsy-proven axillary node involvement and convert their axillary nodes to ypN0 after NC, CWI+RNI after mastectomy, or WBI+RNI after BCS, did not significantly improve IBC-RFI, LRRFI, DRFI, DFS, or OS. These findings suggest that downstaging involved axillary nodes with NC can result in optimization of adjuvant radiotherapy without adversely affecting oncologic outcomes. Follow-up of pts for long-term outcomes continues. NCT01872975 *EPM and JW are co-first authors. Table 1 Citation Format: Eleftherios Mamounas, Hanna Bandos, Julia White, Thomas Julian, Atif Khan, Simona Shaitelman, Mylin Torres, Frank Vicini, Patricia Ganz, Susan McCloskey, Nilendu Gupta, X. Allen Li, Peter Lucas, Nadeem Abu-Rustum, Saumil Gandhi, Rahul Tendulkar, Robert Coleman, Keiichi Fujiwara, Samantha Seaward, William Irvin, Kristin Higgins, Robert Mutter, Jean-Francois Boileau, Andrew Muskovitz, Reshma Jagsi, Anna Weiss, Curran Walter Jr., Norman Wolmark. Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304 [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 GS02-07.

Abstract PO2-23-10: Obesity May Modulate the Relationship Between High Mammographic Breast Density and Neoadjuvant Chemoresistance in Early Breast Cancer

Abstract Background - An inverse association has been described in a number of studies between mammographic breast density (MBD) and pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for early breast cancer (BC), implicating high MBD in chemotherapy resistance. However, this effect has not been seen in all there is a paucity of data exploring whether this relationship extends the relationship beyond pCR to overall survival. This study aims to validate the relationship between MBD and pCR in patients undergoing NAC for early BC as well as to assess the relation of MBD with clinical complete response (cCR), relapse-free (RFS) and BC-specific survival (BCSS). Further, this study examines these associations stratified by body mass index (BMI). Methods - MBD was measured in contralateral mammograms in 127 women before NAC, using Cumulus software. As the study spanned the transition period from film to digital mammography, film mammograms were digitised using a high-powered scanner and processed full-field digital mammograms were extracted from the imaging storage facility. Basic patient, tumour and treatment demographics were collated including BMI. Percent dense area (PDA) was correlated with patient and tumour characteristics, short-term (pCR/cCR incidences), and long-term chemotherapy outcomes (RFS and BCSS). Results - Overall rates of cCR and pCR of 49% and 21% were observed across the whole cohort. Mean PDA was higher in those not undergoing cCR (p=0.041) and relapsing patients (p=0.041) but did not significantly vary by pCR or BC-deaths. As a dichotomous variable, high PDA relative to low PDA corresponded to lower cCR (40 v 58%, p=0.027), but no significant difference was seen for pCR (17.5 v 25.0%, p=0.15), BC relapse (38 v 30%, p=0.15) or BC-death (32 v 25%, p=0.20). High PDA (relative to low PDA) in patients with obesity (BMI &amp;gt;30kg/m2) was associated with lower pCR (0% v 28.1%, p=0.036) and numerically higher relapse rates (56% v 28%, p=0.063) and breast cancer deaths (56 v 28%, p=0.071. No such relationship was observed in patients with a BMI&amp;lt; 30kg/m2. Conclusion - Higher MBD associated with lower cCR and higher relapse but not with pCR or BC death. The inferior outcomes with high MBD were confined to patients with obesity in our study. Further analysis of the relationship between MBD and outcomes, including by BMI, is warranted. Citation Format: Andrew Redfern, Veenoo Agarwal, Ellie Darcey, Lisa Spalding, Hilary Martin, Jennifer Stone. Obesity May Modulate the Relationship Between High Mammographic Breast Density and Neoadjuvant Chemoresistance in Early Breast Cancer [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 PO2-23-10.

Abstract PO2-18-11: Short-term Pre-OPerative Durvalumab (MEDI 4736) in early small triple negative breast cancer patients (POP-Durva)

Abstract Background: Immune checkpoint inhibitors (ICIs) are one of the major therapeutic advancements in cancer treatment. Anti-programmed cell death protein 1 (Anti-PD1)/PD-L1 ICIs have improved progression-free survival in patients with metastatic triple negative breast cancer (TNBC) and pathologic complete response (pCR) and event-free survival in patients with early TNBC. Nevertheless, some patients treated with anti-PD(L)1 ICIs experience recurrence or do not achieve sustained clinical benefit. In addition, very interesting data show the existence of a subgroup of patients with exceptional tumour responses to monotherapy with anti-PD(L)1 ICIs. These exceptional responses are observed in various tumour types, such as colorectal or breast cancer. Although in colorectal cancer, the determinants for this extreme sensitivity to immunotherapy treatment are identified (existence of MSI) in breast cancer, this is not the case. There is still a lack of knowledge about predictive biomarkers and mechanisms of action for ICIs. Trial Design: POP-Durva (NCT05215106) is a prospective, one-arm-only study aiming at determining the pCR rate after two administrations of Durvalumab monotherapy in patients with stage I TNBC. This window-of-opportunity study will recruit 195 consecutive cases of stage I TNBC (ER &amp;lt; 1%, PR &amp;lt; 1%, HER2 negative) and TILs≥5%, eligible for short-term treatment with durvalumab. Study treatment consists of two administrations of intravenous Durvalumab monotherapy, 10mg/kg, at two weeks intervals. After study treatment, patients will receive a standard treatment strategy (surgery or neoadjuvant systemic treatment) as per physician choice. The primary endpoint is the pCR rate after treatment with Durvalumab, defined as the absence of invasive disease in the breast and negative axillary nodes (ypT0/yTis ypN0). Assessment of the primary endpoint will be performed at the surgery or at the biopsy at the end of treatment) for patients undergoing neoadjuvant treatment. For patients in whom neo-adjuvant therapy is the first standard treatment strategy (i.e. after study treatment) a breast ultrasound-guided biopsy is mandatory at the end of the treatment visit. If the biopsy-proven residual disease is demonstrated, patients can receive standard neoadjuvant therapy at the discretion of the treating investigator. Patients with biopsy-proven residual disease will be considered as having no pCR. Those with a complete response may proceed directly to surgery. The expected pCR rate with Durvalumab monotherapy is 20%. The sample size of 195 patients will allow us to estimate this expected pCR rate with a 95% confidence interval of a precision of 6.2%. Secondary objectives are objective response rate and safety. Exploratory objectives are to: a. describe immune cell dynamics associated with exceptional responses to ICI (using spectral cytometry analysis), b. describe somatic genetic contributions to the determination of immune responsiveness (using whole exome sequencing (WES) and in a subset of patient's single-cell RNA-seq), c. characterize tumour cells – immune cells' interaction/spatial distribution(using imaging mass cytometry), d. explore the association between gut microbiome composition/signatures predictive of response to ICI (using 16s rRNA sequencing) and e. identify predictive tissue/blood-based biomarkers of response and to anti-PD(L)1 ICIs therapy. A total of two dedicated FFPE samples and two fresh biopsies will be collected at the time of inclusion and at the end of treatment biopsy or on the surgical specimen. In addition, we will collect stool samples pre and at the completion of all Durvalumab treatments and blood samples at the time of inclusion, during treatment (before each Durvalumab administration) and at the end of treatment for serum and plasma extraction and whole blood to serve as a control for WES. Citation Format: Joana Mourato Ribeiro, Isabelle Pic, Quentin Blampey, Elie Rassy, Nusaibah Ibrahimi, Laura Salabert, Olivier Trédan, Monica Arnedos, Semih Dogan, Kamar Serhal Serhal, Clementine Mahaut, Alessandro Viansone, Salim Laghouati, Barbara Pistilli, Charles-Antoine Dutertre, Magali Lacroix-Triki, Jean-Yves Scoazec, Lisa Derosa, Laurence Zitvogel, Corinne Balleyguier, Nadege Bercovici, Paul-Henry Cournede, Stefan Michiels, Fabrice André. Short-term Pre-OPerative Durvalumab (MEDI 4736) in early small triple negative breast cancer patients (POP-Durva) [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 PO2-18-11.

Abstract PO1-03-11: Camrelizumab in Combination with Nab-Paclitaxel and Carboplatin versus Nab-Paclitaxel and Carboplatin as Neoadjuvant Therapy for Triple Negative Breast Cancer: A Multicenter, Open-Label, Randomized Controlled Study

Abstract Background: Triple-negative breast cancer (TNBC) is recognized for its aggressive nature and unfavorable prognosis. Immune checkpoint inhibitors have demonstrated promising antitumor activity in both neoadjuvant and metastatic settings. This study aimed to assess the efficacy and safety of camrelizumab, an anti-PD-1 antibody, in conjunction with chemotherapy as a neoadjuvant treatment for early-stage TNBC. Methods: This two-phase prospective, multicenter, randomized controlled study was initiated with the enrollment of previously untreated stage II-III TNBC patients in the first phase. They received neoadjuvant therapy comprising six 3-week cycles of camrelizumab (200 mg, q3w), along with nab-paclitaxel (220 mg/m2, q3w) and carboplatin (AUC 5, q3w). In the second phase, patients were enrolled and randomized 1:1 to either the camrelizumab plus nab-paclitaxel and carboplatin group or the nab-paclitaxel plus carboplatin group. The present report covers the data from the first phase of the study. The primary endpoint was the total pathological complete response (tpCR, ypT0/is ypN0) rate. Secondary endpoints included breast pathological complete response (bpCR, ypT0/is) rate, objective response rate (ORR), event-free survival (EFS), residual cancer burden (RCB), and safety. This study is registered with ClinicalTrials.gov, under the identifier NCT04907344. Results: Between September 2021 and March 2023, 39 patients were enrolled in the first phase. A total of 35 (89.7%) were node-positive. Among the 32 patients with evaluable efficacy, the tpCR rate was 59.4% (19/32), and the bpCR rate was 68.8% (22/32). The ORR at the end of neoadjuvant treatment stood at 87.2% (34/39). Among the 39 patients, 11 (28.2%) experienced grade 3 or higher treatment-related adverse events, the most common of which were thrombocytopenia (6 [15.4%]), leucopenia (5 [12.8%]), neutropenia (5 [12.8%]), alanine aminotransferase increased (2 [5.1%]), aspartate aminotransferase increased (1 [2.6%]), and hypothyroidism (1 [2.6%]). Adverse events leading to discontinuation of any agent occurred in 5 (12.8%) patients, while adverse events leading to delay in treatment occurred in 7 (17.9%) patients. Serious treatment-related adverse events were reported by 4 (10.4%) patients. Conclusions: In patients with early TNBC, the neoadjuvant treatment of camrelizumab in combination with nab-paclitaxel and carboplatin demonstrated a high pCR rate with an acceptable safety profile. The second phase of the study is currently in progress to validate these findings. Citation Format: Weipeng Zhao, Xin Wang, Bin Zhang, Yehui Shi, Chen Wang, Xu Wang, Shufen Li, Chunfang Hao, Ning Lu, Yongsheng Jia, Li Zhang, Lan Zhang, Weixin Sun, Xuchen Cao, Zhongsheng Tong. Camrelizumab in Combination with Nab-Paclitaxel and Carboplatin versus Nab-Paclitaxel and Carboplatin as Neoadjuvant Therapy for Triple Negative Breast Cancer: A Multicenter, Open-Label, Randomized Controlled 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 PO1-03-11.

Abstract PO1-27-01: Comparing the Efficacy and Safety of TQB2440 versus the Reference Pertuzumab for the Treatment of HER2-Positive Early or Locally Advanced Breast Cancer: A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase 3 Trial

Abstract Background: Pertuzumab is a recombinant humanized monoclonal antibody targeting the extracellular dimerization domain II of HER2. On September 30, 2013, the FDA have granted accelerated approval of a pertuzumab regimen for neoadjuvant treatment of patients (pts) with high-risk, HER2-positive early stage breast cancer. TQB2440 is a pertuzumab (Perjeta®, Roche) biosimilar. This study aimed to compare the efficacy and safety of TQB2440 and the reference pertuzumab combined with trastuzumab and docetaxel in pts with HER2-positive early or locally advanced breast cancer. Methods: In this multicenter, randomized, double-blind phase 3 study, eligible pts were aged 18-75 with operable HER2-positive (IHC 3+ or ISH+) clinical stage II-IIIC breast cancer negative for ER/PR and had an ECOG PS of 0-1. The pts were randomly assigned to receive either TQB2440 or the reference pertuzumab (Perjeta®) (840 mg on day 1, cycle 1, followed by 420 mg on cycle 2-4, q3w) added to trastuzumab (8 mg/kg on day 1, cycle 1, followed by 6 mg/kg for cycles 2-4, q3w) + docetaxel (75 mg/m2, cycle 1-4, q3w). The pts then underwent surgery followed by adjuvant treatment with FEC regimens (fluorouracil 600 mg/m², epirubicin 90 mg/m², cyclophosphamide 600 mg/m², cycle 5-7, q3w), then TQB2440 (840 mg on day 1, cycle 8, followed by 420 mg on cycle 9-20, q3w) + trastuzumab (8 mg/kg on day 1, cycle 8, followed by 6 mg/kg for cycles 9-20, q3w) or until disease progression or intolerable toxicity. The primary endpoint was total pathologic complete response (tpCR) by independent review committee (IRC). Equivalence was established if the 90% confdence intervals (CIs) of the relative ratio [RR] within the interval of 0.76 to 1.32. Secondary endpoints included breast pathologic complete response (bpCR) by IRC, tpCR &amp; bpCR by investigator, breast conserving surgery (BCS) rates, objective response rate (ORR), event-free survival (EFS), disease-free survival (DFS), OS and safety. Results: Between October 21, 2020, and November 21, 2022, 412 pts were enrolled (TQB2440 group, n=207; the reference pertuzumab group, n=205). Data cutoff was November 30, 2022. In the intention-to-treat (ITT) population, the tpCR by IRC of the TQB2440 group and the reference drug group were 58.94% and 58.05%, respectively. The RR was 1.02 (90% CI, 0.89, 1.16), which was within the predefined equivalence interval of 0.76 to 1.32. There was no statistically significant difference in the bpCR by IRC between the TQB2440 group and the reference pertuzumab group (67.63% [95% CI, 60.80%, 73.95%] vs. 63.90% [95% CI, 56.92%, 70.48%], P=0.4249). The BCS rate also comparable between the two groups with 13.04% (95% CI, 8.77%, 18.41%) vs. 13.17% (95% CI, 8.86%, 18.58%) (P=0.9695). Additionally, the results of the PP (per-protocol) population were similar to those of the ITT population. The incidence of treatment-related adverse events (TRAEs) and grade ≥3 TRAEs were similar between the TQB2440 group and the reference pertuzumab group with 79.71% vs. 75.98% and 49.28% vs. 41.67%, respectively. Conclusion: In patients with HER2-positive early or locally advanced breast cancer, TQB2440 demonstrated equivalent efficacy and similar safety to the reference pertuzumab. Clinical trial information: NCT05985187. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd Citation Format: Qingyuan Zhang, Shusen Wang, Nanlin Li, Qiao Cheng, Yu ren, Xuchen Cao, Jianjun Huang, Caigang Liu, Hongwei Yang, Limin Wei, Zhangjun Song, Huadong Zhao, Fangling Ning, Xiaojia Wang, Dehong Zou, Xiaohua Zeng, Jie Hao, Yunjiang Liu, Huijuan Wang, Nie Jianyun, Liang Li, Lina Liu, Tao Sun, Xiaobo Hu, Zhenhua Zhai, Huihua Xiong, Yuanqi Zhang, Enxiang Zhou, Jing Sun, Zhenhai Cai, Antai Zhang, Shui Wang, Junyang Mo, Qun Su, Xiuheng Qi, Guoren Zhou, Shuqun Zhang, Guozhong Cui, Wei Wang, Mingjiang Fan, Xinyu Qian, Xinhong Wu, Zhihong Wang, Jiuda Zhao, Yonghui Luo, Yanming Zhang, Fuguo Tian, Jiye Zhang, Dongning Chai, Qingshan Li. Comparing the Efficacy and Safety of TQB2440 versus the Reference Pertuzumab for the Treatment of HER2-Positive Early or Locally Advanced Breast Cancer: A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase 3 Trial [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 PO1-27-01.

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.

Breast surgery after neoadjuvant systemic therapy.

For patients with operable breast cancer, neoadjuvant systemic therapy (NST) can be used to downstage the primary tumor in the breast and to facilitate breast-conserving surgery (BCS) in patients with large tumors who desire breast conservation. Rates of breast pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) are highest in patients with triple-negative and human epidermal growth factor receptor 2 (HER2) positive (HER2+) disease; however, achieving pCR is not necessary for successful downstaging and avoidance of mastectomy, and rates of conversion to BCS-eligibility are high across all receptor subtypes. Neoadjuvant endocrine therapy (NET) can be used instead of NAC in postmenopausal patients with hormone receptor positive (HR+)/HER2 negative (HER2-) breast cancer to downstage the breast, particularly when the patient has no clear indication for systemic chemotherapy, but desires breast conservation. In patients treated with NET, rates of conversion to BCS-eligibility are similar to rates observed with NAC. The oncologic safety of BCS after NAC and NET has been established in prospective trials, and local recurrence (LR) rates are acceptably low provided negative surgical margins can be obtained. Investigation is under way to determine the feasibility and safety of omitting breast surgery in patients with responsive subtypes who have no residual invasive or in situ disease identified on post-treatment tumor bed biopsies; however, the significant risk of missing residual disease-which may impact selection of adjuvant systemic therapy-may preclude future adoption of this approach.

Mammographic density changes after neoadjuvant chemotherapy in triple-negative breast cancer: Association with treatment and survival outcome

PurposeTo investigate the association of mammographic breast density with treatment and survival outcomes in patients with triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NAC). MethodsThis retrospective study evaluated 306 women with TNBC who underwent NAC followed by surgery between 2010 and 2019. The baseline density and the density changes after NAC were evaluated. Qualitative breast density (a-d) was evaluated using the Breast Imaging Reporting and Data System. Quantitative breast density (%) was evaluated using fully automated software (the Laboratory for Individualized Breast Radiodensity Assessment) in the contralateral breast. Multivariable logistic regression analysis was used to evaluate the association between breast density and pathologic complete response (pCR), stratified by menopausal status. Cox proportional hazard regression analysis was used to evaluate the association among breast density, the development of contralateral breast cancer, and the development of locoregional recurrence and/or distant metastasis. ResultsContralateral density reduction ≥10 % was independently associated with pCR in premenopausal women (odds ratio [OR], 2.5; p = 0.022) but not in postmenopausal women (OR, 0.9; p = 0.823). During a mean follow-up of 65 months, 10 (3 %) women developed contralateral breast cancer, and 68 (22 %) women developed locoregional recurrences and/or distant metastases. Contralateral density reduction ≥10 % showed no association with the occurrence of contralateral breast cancer (hazard ratio [HR], 3.1; p = 0.308) or with locoregional recurrence and/or distant metastasis (HR, 1.1; p = 0.794). ConclusionIn premenopausal women, a contralateral breast density reduction of ≥10 % after NAC was independently associated with pCR, although it did not translate into improved outcomes.

Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Human Epidermal Growth Factor 2-Positive/Triple-Negative Breast Cancer Patients With Excellent Response.

The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT. ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1-3N0-1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life. Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients. ClinicalTrials.gov Identifier: NCT04993625. Registered on August 6, 2021. Clinical Research Information Service Identifier: KCT0006371. Registered on July 22, 2021.

Comparing extracellular volume fraction with apparent diffusion coefficient for the characterization of breast tumors

PurposeTo investigate the feasibility of dual-energy CT (DECT)-derived extracellular volume (ECV) fraction for characterization of breast tumors, compared to apparent diffusion coefficient (ADC) and validated against histopathological findings. Material and methodsThe ECV fraction and ADC were prospectively assessed in patients with breast tumors using chest DECT and breast MRI. The diagnostic performance of ECV fraction and ADC was accessed in predicting breast histopathological subtypes and pathological complete response (pCR) status. Histopathological sections were analyzed by digital image analysis. Pearson’s correlation analysis was used to correlate between DECT and histopathological ECV fractions. ResultsThis study included 271 patients, with 314 breast lesions (61 benign and 253 malignant). The ECV fraction and ADC showed comparable area under the curve (AUC) for distinguishing benign from malignant lesions (p = 0.123) and invasive carcinoma from ductal carcinoma in situ (p = 0.115). There were significant differences in ECV fraction between different hormone receptors and Ki67 states (p = 0.001 ∼ 0.014), while ADC values only differed among various Ki67 states (p < 0.001). The ECV fraction was lower (p = 0.007), ADC was higher (p = 0.013) in pCR than in non-pCR group, with an AUC of 0.748 and 0.730 (p = 0.887), respectively. There was a positive correlation between DECT and histopathological ECV fractions (r = 0.615, p < 0.01). ConclusionsRoutine chest DECT-derived ECV fraction is a viable quantitative imaging biomarker for predicting histopathological subtypes and pCR in patient with breast tumors, and correlated well with histopathology finding.

Neoadjuvant pyrotinib plus trastuzumab and chemotherapy for HER2-positive breast cancer: a prospective cohort study

BackgroundThis prospective study aims to investigate the efficacy and safety of pyrotinib (P) combined with 4 cycles of epirubicin and cyclophosphamide followed by 4 cycles of taxane and trastuzumab (P + EC-TH) regimen as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer and to investigate the predictive value of p53, p63, and epidermal growth factor receptor (EGFR) status for neoadjuvant efficacy.MethodsA total of 138 HER2-positive breast cancer patients who received neoadjuvant therapy and underwent surgery were included. Case group: 55 patients received P + EC-TH regimen. Control group: 83 patients received EC-TH regimen. The chi-square test, Fisher’s exact test, and logistic regression analysis were applied. The primary endpoint was total pathologic complete response (tpCR), and the secondary endpoints were breast pathologic complete response (bpCR), overall response rate (ORR), and adverse events (AEs).ResultsIn the case group, the tpCR rate was 63.64% (35/55), the bpCR rate was 69.09% (38/55), and the ORR was 100.00% (55/55). In the control group, the tpCR rate was 39.76% (33/83), the bpCR rate was 44.58% (37/83), and the ORR was 95.18% (79/83). The case group had significantly higher tpCR and bpCR rates than those of the control group (P < 0.05), but there was no significant difference in ORR (P > 0.05). The tpCR was associated with the status of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), and the patients with any negative ER, PR, AR, or combined, were more likely to achieve tpCR than those with positive results (P < 0.05). The p53-positive patients were more likely to achieve tpCR and bpCR than p53-negative patients (P < 0.05). The incidence of hypokalemia and diarrhea in the case group was higher than that in the control group (P < 0.05). The AEs developed were all manageable, and no treatment-related death occurred.ConclusionThe efficacy and safety of the P + EC-TH regimen were verified by this study. The HER2-positive breast cancer patients treated with the EC-TH neoadjuvant regimen were more likely to achieve tpCR or bpCR if pyrotinib was administered simultaneously.

Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials

The identification of prognostic markers in patients receiving neoadjuvant therapy is crucial for treatment optimization in HER2-positive breast cancer, with the immune microenvironment being a key factor. Here, we investigate the complexity of B and T cell receptor (BCR and TCR) repertoires in the context of two phase III trials, NeoALTTO and CALGB 40601, evaluating neoadjuvant paclitaxel with trastuzumab and/or lapatinib in women with HER2-positive breast cancer. BCR features, particularly the number of reads and clones, evenness and Gini index, are heterogeneous according to hormone receptor status and PAM50 subtypes. Moreover, BCR measures describing clonal expansion, namely evenness and Gini index, are independent prognostic factors. We present a model developed in NeoALTTO and validated in CALGB 40601 that can predict event-free survival (EFS) by integrating hormone receptor and clinical nodal status, breast pathological complete response (pCR), stromal tumor-infiltrating lymphocyte levels (%) and BCR repertoire evenness. A prognostic score derived from the model and including those variables, HER2-EveNT, allows the identification of patients with 5-year EFS > 90%, and, in those not achieving pCR, of a subgroup of immune-enriched tumors with an excellent outcome despite residual disease.

A machine learning-based algorithm to eliminate breast and axillary surgery in patients with breast cancer and pathological complete response after neoadjuvant chemotherapy

Alexandre de Nonneville, Laurys Boudin, Gilles Houvenaeghel, Anthony Gonçalves, François Bertucci

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.

Treatment efficacy score: a better surrogate for arm-level survival differences in neoadjuvant breast cancer trials?

Neoadjuvant chemotherapy is widely used in the therapy of stage II-III breast cancers and pathologic complete response (pCR; ypT0/is, ypN0) predicts excellent long-term survival. However, the correlation between improvement in pCR rate and survival is highly variable across trials. A major limitation of pCR is that it does not capture downstaging in patients with residual disease. We previously introduced the residual cancer burden (RCB) score that measures pathologic response on a continuous scale. Comparison of RCB score distributions between trial arms reflects treatment efficacy more accurately than differences in pCR rate. We developed the treatment efficacy score (TES) as a new statistical metric that appears to be a better surrogate for trial arm-level survival improvement than pCR rate difference.

Distinct Prognosis of Minimal Residual Disease According to Breast Cancer Subtype in Patients with Breast or Nodal Pathologic Complete Response After Neoadjuvant Chemotherapy.

Few studies have reported on patient prognosis according to residual cancer burden after neoadjuvant chemotherapy (NAC). Herein, we evaluated the survival of patients based on residual disease after NAC to identify subpopulations with distinct prognoses. We retrospectively reviewed 728 patients treated with NAC from 2010 to 2017. Patients were divided into four subgroups depending on post-surgical residual disease according to the staging system: pathological complete response (pCR) (ypT0/TisN0), minimal residual disease (MRD) (ypT1mi/T1aN0 or ypT0/Tis ypN0i+/N1mic), node-only pCR (≥ ypT1b ypN0), and breast-only pCR (ypT0/Tis ≥ ypN1a). Clinicopathological characteristics and survival outcomes were analyzed by adjusting for factors affecting survival. Overall, 50.4% (n = 367) of patients achieved pCR, with the MRD group accounting for 16.5% (n = 120). Although age and clinical stage were not different among the study groups, histologic grade, subtypes, chemotherapy response, and local treatment showed differences. Event-free survival (EFS) and overall survival (OS) demonstrated no significant difference between the pCR and MRD groups. In the multivariate analysis, pCR status was the only significant factor in EFS, and no statistical difference was noted between the pCR and MRD groups. However, clinical stage, pCR status, and subtype significantly affected the OS. MRD showed favorable outcomes in terms of both EFS and OS in all subtypes, except for those with triple-negative breast cancer (TNBC). Patients with MRD showed outcomes comparable to those of patients who achieved pCR and may be candidates for de-escalation of post-NAC treatment, except for those with a TNBC subtype.