tbuckley/cabot-search huggingface dataset:
Results of neoadjuvant therapy for patients with triple negative breast cancer in a public hospital in Brazil (Federal District).
Authors: Rafael Amaral De Castro, Fernanda das Neves Carneiro Haum, Andrew Sá Nunes, Patricia Werlang Schorn
Journal: Journal of Clinical Oncology (2024)

e12660 Background: Breast cancer is the neoplasm with the highest number of deaths among women in Brazil. Triple negative breast cancer contributes to the worsening of this condition, considering that it is more aggressive, accounting for 15% of deaths. Furthermore, more aggressive treatments and new medications have recently been added to neoadjuvant protocols, improving the complete pathological response, but with more side effects. In this way, it is predictive to understand the profile and treatment of choice for patients diagnosed with triple negative breast cancer, contributing to a better understanding of the treatment outcome, survival and quality of life in patients with this health condition. Methods: observational and cross-sectional study with retrospective data collection, in the electronic medical record of the TrakCare system. Patients diagnosed with triple-negative breast cancer between January 2020 and December 2021 and who underwent neoadjuvant treatment were included. Information was collected regarding the date of treatment, age, color/race, comorbidity, staging, type of chemotherapy used, postoperative response rate, and patient evolution during follow-up. Results: 78 patients with triple-negative breast cancer were included. The average age of patients was 56.3 years (26 – 83 years) and approximately 38.5% of patients were under 50 years of age. Around 42.3% of patients had hypertension and 33.3% were obese. Only 28.2% of patients did not have associated comorbidities. Approximately 59% of patients were staged T4 and 35.9% staged T3. Pathological complete response (cPR) was achieved in 56.4%, but progression was recorded in 13% of cases. In 88.5% of patients, the AC-T protocol was used (doxorubicin and cyclophosphamide followed by weekly paclitaxel) and 52% obtained CPR. On the other hand, only 11.5% (9 patients) used the AC-TC protocol (doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin) with a CPR of 89% (p=0.016), with no record of progression or death. Conclusions: Triple negative patients were young and tended to have at least one comorbidity in addition to a highest rate of locally advanced tumor. The more aggressive protocol (AC-TC) was used less often, but has a higher rate of cRP and should be used more frequently in this scenario despite the greater complexity of these patients.
Assessing the feasibility and cost-effectiveness of all oral adjuvant chemotherapy (cyclophosphamide, methotrexate, capecitabine) in high-risk hormone receptor positive breast cancer.
Authors: Abiola Falilat Ibraheem, VK Gadi, Kent Hoskins, Amina Chaudhry
Journal: Journal of Clinical Oncology (2024)

TPS616 Background: Women with high-risk HR+/HER2- breast cancer (BCA) receive additional chemotherapy to reduce disease recurrence. Preferred Taxane and Anthracycline based chemotherapy regimens have debilitating side effects such as cardiotoxicity, leukemia, peripheral neuropathy, severe fatigue, alopecia, downtime which are more common in black women thereby necessitating dose reductions. Metronomic cyclophosphamide, methotrexate, 5-fluourouracil (CMF) is an option but less preferred due to frequent dosing and longer therapy duration. Head-to-head comparison of CMF to anthracycline-based chemotherapy conducted 3 decades ago in early-stage BCA showed anthracycline benefit was driven by HER2+ disease with no benefit for HR+/HER2- BCA. Head-to-head comparison trials of CMF and Taxane-based regimen have not been conducted but single institution data suggest similar disease-free and similar overall survival but different toxicity profiles favoring CMF. In our ongoing trial, we converted all three chemotherapy drugs in CMF regimen to an all-oral regimen namely oral Cyclophosphamide, oral Methotrexate, oral Capecitabine (CMC) with the potential benefit of increased patient convenience, decreased costs (oral agents are generic; no chair time; no growth factors), and improved toxicity profile (low rates of grade III neutropenia, no port complications, no alopecia). This trial in progress aims to evaluate the feasibility of oral CMC by measuring the relative dose intensity in addition to the safety and tolerability of oral CMC. We hypothesize that 80% of patients will receive &gt;85% of the intended dose of oral CMC. Methods: This is a Phase II, single arm, non-randomized study enrolling 25 patients with high-risk early-stage HR+ HER2- breast cancer to receive oral CMC regimen based on dose conversion equivalent bioavailability with conventional metronomic CMF chemotherapy. Enrolled patients will receive adjuvant therapy of oral cyclophosphamide 60 mg/m2 PO days 1-21 continuously, Methotrexate 15 mg/m2 PO Day 1, 8, and 15 and Capecitabine 650 mg/m2 PO BID Day 1- 14 to be given every 21 days for 8 cycles. The primary objective is to assess feasibility which is defined as 80% of patients (greater than 20 patients) maintaining a relative dose intensity (RDI) &gt; 85%. The RDI is calculated as the ratio of the actual dose intensity/standard dose intensity; the average RDI for oral CMC regimen is the sum of RDI for each drug divided by 3. This study will be stopped if &gt;25% of patients report Grade 4+ toxicity on oral CMC. The secondary objectives will assess quality of life as reported by the patients and report adverse effects. Clinical trial information: NCT06085742 . [Table: see text]
Neoadjuvant chemotherapy as an indication to preserve nipple areolar complex in advanced breast cancer.
Authors: Sarah Alsafi, Hee Jeong Kim, Tae-Kyung Yoo, Jisun KIM, Sae Byul Lee, Il Yong Chung, Beom Seok Ko, Jong Won Lee, Byung Ho Sohn
Journal: Journal of Clinical Oncology (2024)

e12655 Background: Nipple areolar skin sparing mastectomy (NASSM) has similar oncologic and surgical safety compared to skin sparing mastectomy (SSM) and conventional mastectomy. It provides a superior cosmetic outcome, patient satisfaction and quality of life. With the increasing rate of pathological response rate with neoadjuvant chemotherapy (NAT), nipple preservation can be achieved. The aim of our study is to evaluate whether NASSM is an appropriate surgical procedure for patients in whom there is radiological evidence of extension or involvement of nipple areolar complex (NAC) prior to NAT. Methods: Patients with advanced breast cancer received neoadjuvant chemotherapy and NASSM or SSM between June 2006 and December 2021 at Asan Medical Center were retrospectively reviewed. We excluded patients with metastatic breast cancer on presentation, bilateral cancer and inflammatory breast cancer. Kaplan-Meier survival analysis and Cox proportional hazard models were applied to determine clinicopathological and radiological factors to determine NAC preservation. Our primary objective to assess tumor cells persistence in the NAC after radiological complete response or resolution of extension to NAC. Results: Total of 1,105 patients included. 71.7% of patients underwent NASSM and 17.2% SSM as a final operation. 144 patients (13%) had a change in the pre- NAT type of surgery decision. 83(7.5%) patients had nipple involvement on final pathology. Out of 312 patients who underwent SSM, only 76 patients had nipple involvement on final pathology When comparing patients who had nipple involvement to those who didn’t on final pathology, clinical T &amp; N stage, histologic &amp; nuclear grade, breast cancer subtype, presence of multifocality/multicentric disease on MRI pre or post NAT, distance of mass to NAC and mass size pre and post NAT, the presence of non mass extension to NAC post NAT, NAC thickening on any image pre and post NAT and presentation symptoms of nipple retraction and skin changes were statistically significant. A multivariate regression analysis was performed to compare all the above factors and showed that breast cancer subtype, tumor nipple distance on MRI pre NAT, nipple areolar thickening on MRI pre NAT, clinical response and nipple retraction on MMG post NAT were statistically significant and indicators of nipple involvement on final pathology. Only 8 patients developed NAC recurrence in the NASSM group. Conclusions: NASSM is a safe procedure in patients who had tumor extension to NAC prior to NAT and showed improvement post NAT as evident on MRI. Further prospective studies are needed to establish and criteria to preserve NAC in this subgroup of patients.
Determinants of pathological complete response and tumor regression in high-risk breast cancer treated with neoadjuvant radiotherapy and chemotherapy.
Authors: Jan Haussmann, Wilfried Budach, Carolin Nestle Kraemling, Sylvia Wollandt, Danny Jazmati, Balint Tamaskovics, Stefanie Corradini, Edwin Boelke, Alexander Haussmann, Werner Audretsch, Christiane Matuschek
Journal: Journal of Clinical Oncology (2024)

e12652 Background: Pathological complete response (pCR) is a recognized prognostic indicator in breast cancer patients undergoing neoadjuvant systemic therapy (naST). Known determinants of pCR include intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage, as well as the type of systemic therapy. Incorporating neoadjuvant radiotherapy (naRT) may enhance response rates, disease-free survival, toxicity profiles, and cosmetic outcomes compared to adjuvant radiotherapy. However, the factors influencing pCR and primary tumor regression with the addition of neoadjuvant radiotherapy to chemotherapy are not well-documented. Methods: A retrospective analysis was conducted on 341 patients (cT1-cT4/cN0-N+) who received naRT and neoadjuvant chemotherapy between 1990 and 2003. Treatment included naRT to the breast and, in most cases, to the supra-/infraclavicular lymph nodes, complemented by an electron or brachytherapy boost. NaST was administered either sequentially or concurrently with RT, utilizing various regimens. Univariate and multivariate regression analyses were employed to evaluate the impact of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) and complete primary tumor response (ypT0/Tis). Receiver operating characteristic (ROC) analysis assessed the interval between radiotherapy (RT) and surgical resection (Rx), as well as the radiotherapy dose. Results: Out of 341 analyzed patients, 31.1% achieved pCR. Multivariate analysis revealed that pCR rates were affected by the planned type of resection, breast cancer subtype, primary tumor stage, and the interval between radiation and surgery. The biologically effective dose to the tumor did not significantly impact pCR. Univariate analysis identified age, resection type, breast cancer subtype, clinical tumor stage, and grading as significant factors for primary tumor regression. In the multivariate analysis, resection type, subtype, and clinical tumor stage remained significant. Radiation dose to the tumor and the interval from radiation to surgery were not significant for pCR. However, a longer interval from radiotherapy to resection significantly predicted pCR when treatment factors were included in the model. Conclusions: The factors associated with pCR following combined neoadjuvant chemotherapy and radiotherapy are akin to those identified with neoadjuvant chemotherapy alone. A prolonged interval to surgery may be linked to higher pCR rates. Escalating the dose beyond 60 Gy did not lead to increased response rates.
Predictive markers of complete pathological response to neoadjuvant chemo-immunotherapy in triple negative breast cancer.
Authors: Kaja Cankar, Maša Auprih, Tanja Ovcaricek, Anja Kovac, Natasa Snoj Sarvari, Luka Dobovisek, Simona Borstnar
Journal: Journal of Clinical Oncology (2024)

e12650 Background: Results from the Keynote 522 clinical trial, which played a pivotal role in evaluating the efficacy of neoadjuvant pembrolizumab in combination with chemotherapy (NAICT), showed a significant improvement in pathological complete response (pCR) rates compared with chemotherapy alone. To date, no significant markers have been identified to predict pathological complete response to NAICT. The primary objective was to identify markers, both molecular and clinical, predictive of pCR to NAICT in a real-world clinical setting. Methods: The retrospective analysis included 38 consecutively treated pts with early stage TNBC who received NAICT including pembrolizumab at the Institute of Oncology, Ljubljana (OIL) between 4 January 2022 and 17 October 2023. Data collected from electronic medical records included tumour size, nodal status, UICC stage, BRCA status, systemic immune-inflammation index (SII) before NAICT and before surgery, and frequency and grade of immune-related adverse events (iAEs) (according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5). In pts who completed surgical treatment, response to treatment was assessed by pathological examination of post-treatment surgical specimens. Descriptive statistical methods were used to summarise and describe the main characteristics. Pearson chi-squared test was used to analyse categorical variables and t-test to evaluate associations between continuous variables. Results: Of the 38 pts, 28 completed surgical treatment and were further analysed. Pathohistological examination of post-treatment surgical specimens revealed pCR in 11 pts (39.3%), with residual disease in 17 pts (60.7%). Of the 17 pts without pCR, 11 pts had RCB score 2 (64.7%) and 5 pts had score 3 (29.4%). The distribution of size, nodal status, UICC stage at diagnosis, BRCA status, frequency of iAEs in correlation with pCR is shown in the Table. A borderline correlation was found between pCR and SII at the start of pembrolizumab treatment (p=0.05). Age, tumour size, nodal status, UICC stage, BRCA status, AEs, SII before surgery were not found to be predictive of pCR. Conclusions: SII at the start of pembrolizumab was found to be a borderline significant marker predictive of pCR. Other characteristics evaluated did not correlate with pCR. [Table: see text]
Real life comparison between doxorubicin and cyclophosphamide (AC) dose-dense (dd) and conventional dose AC in patients with triple negative breast cancer (TNBC) under neoadjuvant treatment.
Authors: Flavia Cavalcanti Balint, Monique Celeste Tavares, Isadora Martins de Sousa, Ana Carolina Marin Comini, Italo Barradas e Silva Borges, Matheus Coimbra Barroso, Livia Alexandre Martins, Débora Guilherme de Albuquerque e Rodrigues de Sousa
Journal: Journal of Clinical Oncology (2024)

e12662 Background: High-risk early triple-negative breast cancer (TNBC) is frequently associated with early recurrence and high mortality. Studies suggest a sustained clinical benefit in patients with TNBC who have a pathological complete response (PCR) after neoadjuvant chemotherapy (NACT). The dose-dense (dd) regimen demonstrated improved survival regardless of hormone receptor expression or HER2 status. The doxorubicin and cyclophosphamide (AC) regimen can be performed in (dd), therefore it must include granulocyte growth factors, which may increase costs and toxicities. The object of the study was to evaluate their clinical characteristics and treatment, patients with TNBC, stage I-III who received ACdd in neoadjuvant treatment versus patients who received AC dose conventional (dc). Methods: We performed a retrospective observational cohort study of patients with early TNBC, stage I-III who received neoadjuvant treatment with chemotherapy based on doxorubicin, cyclophosphamide, paclitaxel and carboplatin associated with pembrolizumab. Results: All 82 patients were women 57.3% received ACdd, 30.4% received AC dc. In group ACdd 59.5% had intercurrence related with chemotherapy, in which 17.8% were neutropenic fever and 21.4% had developed different types of infections (ex: diarrhea, pneumonia and others). In these 2 groups all of them had received antibiotic. About 50% of the patients had developed intercurrence because of treatment toxicity and just 3.5% had disease progression. The other group that we evaluated is composed by patients who ACdc, dose Regarding to these group 48% developed any intercurrence during the neoadjuvant treatment, in which 8.3% had neutropenic fever and 25% had different types of infections. All of them earned antibiotic. About clinical and pathological response, the group that earned ACdd 61.7% got complete clinical response and 8.5% had a disease progression during the treatment. In the other arm 68% got complete clinical response and 4% had a progression. Conclusions: AC dd was more prevalent in our series, despite the additional use of granulocyte growth factor, there were more complications in this group and it did not demonstrate better results than those who received conventional dose AC.
Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Patient-reported outcomes (PROs) from the TROPION-Breast01 study.
Authors: Sonia Pernas, Seock-Ah Im, Masaya Hattori, Binghe Xu, Shusen Wang, Yen-Shen Lu, Giuliano Borges, Junji Tsurutani, Komal L. Jhaveri, Qingyuan Zhang, Michelino De Laurentiis, Noelia Martinez-Jañez, Erika P. Hamilton, Hope S. Rugo, Kevin Kalinsky, Sara M. Tolaney, Lei Shi, Sabrina Sharmin Khan, Yanyan Zhu, Aditya Bardia
Journal: Journal of Clinical Oncology (2024)

1006 Background: In the primary analysis of the Phase 3 TROPION-Breast01 study (NCT05104866), Dato-DXd showed a statistically significant and clinically meaningful improvement in progression-free survival vs investigator’s choice of CT (ICC) (HR 0.63 [95% CI 0.52‒0.76]; p&lt;0.0001) (Bardia et al, ESMO 2023). Here we report PROs from TROPION-Breast01. Methods: Patients with inoperable or metastatic HR+/HER2‒ BC, with disease progression on endocrine therapy and for whom endocrine therapy was unsuitable and who had received 1‒2 prior lines of systemic CT, were randomized 1:1 to Dato-DXd (6 mg/kg Q3W, n=365) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine, n=367). PROs were measured at prespecified timepoints, including secondary PRO endpoints of time to deterioration (TTD) in global health status (GHS)/QoL, physical functioning, and pain based on EORTC QLQ-C30, and exploratory PRO endpoints based on additional questionnaires. Results: PRO questionnaire compliance was 82.5% at baseline in both arms and remained similar across arms over time. TTD was delayed in Dato-DXd vs ICC arms for all secondary endpoints. In an analysis of time to first deterioration (primary analysis), median TTD (HR [95% CI]) in GHS/QoL was 3.4 vs 2.1 months (0.85 [0.68–1.06]), physical functioning was 5.6 vs 3.5 months (0.77 [0.61–0.99]), and pain was 3.5 vs 2.8 months (0.85 [0.68–1.07]); in an analysis of time to confirmed deterioration (sensitivity analysis), median TTD in GHS/QoL was 9.0 vs 4.8 months (0.76 [0.58–0.98]), physical functioning was 12.5 vs 6.2 months (0.77 [0.59–1.01]), and pain was 9.0 vs 5.5 months (0.72 [0.55–0.94]). The Table shows TTD in other selected functioning and symptom scales from EORTC. Patient-reported symptomatic AEs (measured by PRO-CTCAE and EORTC) were generally consistent with clinician-reported safety data, and patient-reported treatment tolerability (measured by PGI-TT) was comparable between arms. Conclusions: In TROPION-Breast01, TTD was delayed in the Dato-DXd vs ICC arms for GHS/QoL, physical functioning, pain, and most other symptoms and functioning scales. PRO data complement the improvement in efficacy and manageable safety profile demonstrated with Dato-DXd vs ICC in the primary analysis, supporting Dato-DXd as a potential new, well tolerated therapeutic option in this setting. Clinical trial information: NCT05104866 . [Table: see text]
Systemic inflammatory markers in neoadjuvant pembrolizumab therapy for triple-negative breast cancer: Prognostic insights and nomogram construction.
Authors: Filippo Giovanardi, Chiara Casartelli, Roberto Di Cicilia, Alessandra Bologna, Elisa Gasparini, Gabriella Moretti, Claudia Degli Esposti, Giancarlo Bisagni, Carmine Pinto
Journal: Journal of Clinical Oncology (2024)

e12649 Background: Systemic inflammatory markers derived from peripheral blood cells, such as the neutrophils and lymphocytes ratio (NLR), derived neutrophil lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), and lymphocyte–monocyte ratio (LMR), have shown promise as prognostic markers. Currently, neoadjuvant treatment (NACT) for early triple-negative breast cancer (eTNBC) involves the addition of an immune therapy, and little is known about the variation of these markers in this specific context. Methods: This study evaluated two groups who received NACT for eTNBC in a single third-level cancer center. The first received NACT with EC X4 and a weekly paclitaxel regimen, the second pembrolizumab and NACT. A total of 70 patients were included, 37 patients in the pembrolizumab group. NLR was defined as the absolute blood neutrophil count (N) divided by the absolute lymphocyte count (L), dNLR was defined as the N divided by the derived L (absolute leukocyte count — N), PLR was defined as the absolute platelet count divided by the L, LMR was defined as the L divided by the absolute monocyte count. Association between systemic inflammatory markers and pathological complete response (pCR) was analyzed using statistical tests. Inflammatory markers were evaluated at the time of diagnosis, at the time of chemotherapy regimen change, and 1 week before surgery. The χ2 test or Fisher’s exact test was used for correlation and Student’s t-test to compare different groups. Results: The pCR rates were 60,6% in the standard therapy and 77,8% in the pembrolizumab. There were no significant differences in clinical characteristics between the two groups. NLR, dNLR, PLR and LMR at 6 months showed significant differences compared to baseline levels. dNLR in the immunotherapy group, at the end of therapy, showed statistical significance with the Welch Two Sample t-test with p-value = 0.001. Variables were weighted with respect to the type of treatment and the outcome was assessed as pCR. On the basis of these data, a nomogram was constructed to predict the likelihood of achieving pCR in patients undergoing neoadjuvant pembrolizumab therapy. Conclusions: This study highlights the potential of systemic inflammatory markers as prognostic indicators in patients with eTNBC undergoing NACT. dNLR is a novel biomarker associated with clinical outcome in solid tumors. In this study, for the first time, a correlation was found between the use of pembrolizumab and the change in dNLR and consequently its impact on pCR. A nomogram was constructed to predict the outcome of pCR. [Table: see text]