Clinical Prognostic Stage Research Articles

Rates of Pathologic Complete Response and Overall Survival in Patients with Inflammatory Breast Cancer: A National Cancer Database Study.

Patients with inflammatory breast cancer (IBC) have worse survival compared with stage III non-IBC matched cohorts; however, the prognostic significance of achieving pathologic complete response (pCR) in the setting of IBC is not well described. We evaluated overall survival (OS) between IBC patients and non-IBC patients who achieved pCR. Adult females diagnosed in 2010-2018 with clinical prognostic stage III unilateral invasive breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery were selected from the National Cancer Database. Unadjusted OS from surgery was estimated using the Kaplan-Meier method, and log-rank tests were used to compare groups. Cox proportional hazard models were used to estimate the association of study groups with OS after adjustment for available covariates. The study included 38,390 patients; n=4600 (12.0%) IBC and n=33,790 (88.0%) non-IBC. Overall pCR rates were lower for IBC compared with non-IBC (20.7% vs. 23.3%; p<0.001). Among those achieving pCR, 5-year mortality was higher for IBC patients (16.4%, 95% confidence interval [CI] 13.9-19.1%) versus non-IBC patients (9.1%, 95% CI 8.4-9.8%; log-rank p<0.001). Among all patients achieving pCR, IBC remained associated with worse OS compared with non-IBC (hazard ratio 1.48, 95% CI 1.19-1.85; p<0.001). We found a lower pCR rate and worse OS in IBC patients compared with non-IBC stage III patients. Despite effective systemic therapies, achieving a pCR for IBC patients may not carry the same prognostic impact compared with non-IBC stage III patients.

Abstract PO1-01-03: Pathological response according to early metabolic remission in an interim FDG-PET scan and to tumor infiltrating lymphocytes - A secondary analysis of the phase II trial ABCSG 52/ATHENE investigating atezolizumab in early HER2+ BC

Abstract Background: ABCSG-52/ATHENE investigated a neoadjuvant chemotherapy de-escalation/immunotherapy escalation approach with trastuzumab, pertuzumab, atezolizumab and epirubicin for early-stage HER2-positive breast cancer. The pathological complete response rate (pCR; ypT0/Tis, ypN0) - the primary endpoint of the trial - was 60.3% (95% CI 47.5% - 71.9%), and was higher than the predefined threshold for positivity (≥ 40%). Interestingly, higher pCR rates were observed in PD-L1 immune cell (IC) negative tumors (pCR 69.2%) as compared to PD-L1 IC positive tumors (pCR 55.2%). No new safety concerns were observed. Primary outcome data were reported at the ESMO Breast Cancer Conference 2023. Here, we present the correlation of pathological outcome according to early metabolic response in an interim fluorodeoxyglucose F18 positron emission tomography (FDG-PET) scan, and according to stromal tumor infiltrating lymphocytes (TILs) at baseline. Methods: Patients (pts) with previously untreated, histologically confirmed HER2-positive early breast cancer (EBC; clinical prognostic stage cT1c-4a-d, N0–3, M0) were randomized 1:1 to two 3-weekly cycles of a chemotherapy-free induction phase (Part 1) with trastuzumab and pertuzumab (TP) plus 1200 mg atezolizumab (TP+A), or TP alone. Subsequently, all pts received 4 cycles of TP+A in combination with epirubicin 90 mg/m² (Part 2). Randomization was stratified according to baseline TILs (&amp;lt; 5% vs ≥ 5%), hormone receptor status (positive vs. negative), and prognostic stage (≤ IIA vs. ≥ IIB; AJCC v.8.0). An FDG-PET assessment was performed at baseline and after 2 cycles of study treatment. According to PERCIST, early metabolic responses were classified as metabolic complete response (mCR) and metabolic partial response (mPR) and association with outcome was tested with Fisher’s exact test. TIL assessment in pretreatment biopsy specimen were performed according to the recommendations from the International TILs Working Group. Lymphocytic predominant phenotype was defined as a TIL proportion of ≥ 50%. Correlation of TILs and pCR was modeled with logistic regression. Results: Overall, 58 pts were randomized to TP-A (n=29) or TP (n=29) at 9 sites. In 45 patients, a protocol predefined PERCIST assessment was available. An early mCR was achieved in 14 pts (n=14/45, 31.1%): 5 pts (n=5/21, 23.8%) in the TP group and 9 pts (n=9/24, 37.5%) in the TP-A group. Pts with and without an early mCR achieved a pCR in 92.9% (n=13/14) and 54.8% (n=17/31) of cases (p=0.016), respectively. An early mCR/mPR was achieved in 37 pts (n=37/45, 82.2%). Pts with and without an early mCR/mPR achieved a Residual Cancer Burden (RCB) class 0 or I in 89.2% (n=33/37) and 50.0% (n=4/8) of cases (p=0.024), respectively. The mean stromal TIL proportion was 23.9% in the overall population, with 22.8% in TP group and 25.0% in TP-A group. A lymphocytic predominant phenotype was seen in 10.3% of pts treated in the TP group, and 17.2% of pts treated in the TP-A group. No association between TIL proportion at baseline and pCR could be detected (OR for a 10%-point increase = 1.02, 95% CI 0.78-1.34). A moderate positive correlation between numeric values of TILs and PD-L1 ICs was observed (spearman r=0.57, P&amp;lt; 0.0001). Exploratory correlation analyses of PD-L1 status, TIL proportion and metabolic responses in interim FDG-PET scans will be presented at the meeting. Conclusions: In ABCSG-52, chemotherapy de-escalation with intensified immunotherapy was effective and safe. Early metabolic response assessment was feasible and predicted pathologic response; therefore, incorporation of interim FDG-PET results into de-escalation trials merits further investigation. In contrast to regimens without immune-checkpoint inhibitors, TIL proportion at baseline did not correlate with pathological outcome. Funding: Provision of IMP and financial support by Roche Austria GmbH Citation Format: Gabriel Rinnerthaler, Daniel Egle, Rupert Bartsch, Clemens Schmitt, Andreas Petzer, Marija Balic, Edgar Petru, Ursula Denison, Christian F. Singer, Vesna Bjelic-Radisic, Simon Gampenrieder, Michael Knauer, Karl Sotlar, Christine Brunner, Florian Posch, Dominik Hlauschek, Lidija Sölkner, Zsuzsanna Bago-Horvath, Martin Filipits, Manuela Gili, Michael Gnant, Richard Greil. Pathological response according to early metabolic remission in an interim FDG-PET scan and to tumor infiltrating lymphocytes - A secondary analysis of the phase II trial ABCSG 52/ATHENE investigating atezolizumab in early HER2+ BC [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 PO1-01-03.

The Effect of Clinical (Anatomical) and Prognostic Stage Groups on Survival in Patients Diagnosed with Breast Cancer: MULTI-Center Study Results, TROD Breast Cancer Study Group

The American Joint Committee on Cancer (AJCC) anatomic stage groups have arguably been the most powerful method in predicting breast cancer outcomes. In the present study, we aimed to determine the differences between anatomical stage and clinical prognostic stage groups, which were obtained by adding biological markers such as histologic tumor grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 status to patients diagnosed with breast cancer, the rate of change in stage, and the effect of stage change on survival. The study protocol was sent to all radiation oncology centers in Türkiye. Four centers enrolled their patients to the study. A total of 1470 stage I-III breast cancer patients with complete information on biological markers (histologic tumor grade, hormone receptor, and c-erb B2 receptor status), haven't been treated with neoadjuvant therapy were included to the study and evaluated retrospectively. The 8th edition of AJCC consolidated biological markers in to clinical prognostic stage groups. Kaplan-Meier curves were used to estimate survival. The log-rank test was used to compare the difference between groups. The Cox proportional-hazards regression model was used to determine the association between anatomic-prognostic stage, disease-free survival (DFS), and overall survival (OS). The median follow-up time was 82 (6-237) months. Median age of the patients was 52 years (20-88) and 865 cases (58.8%) were in the postmenopausal period. The axillary lymph node status was negative (N0) in 765 patients (52.1%). Tumor grade was grade I in 200 patients (13.6%), grade II in 812 patients (55.2%) and grade III in 452 patients (30.7%). Estrogen receptor status was positive in 1247 patients (84.8%), PR status was positive in 1178 patients and Her2-neu status was positive in 207 patients (14.1%). A stage change has been identified in a total of 777 patients (52.9%). Compared with the anatomic stage groups, application of the clinical prognostic stage groups assigned 46.4% cases lower and 6.5% cases higher stage. Five- and ten-year OS and DFS rates of the patients are 73.7%, 44.3% and 91.9%, 86.3% respectively. Age (p<0.001), tumor grade (p<0.001), ER status (p<0.001), PR status (p<0.001), cerbB2 receptor status (p = 0.025) were found to be statistically significant variables in multivariable analysis for OS. For DFS, multivariable analysis showed that age (p = 0.027), tumor grade (p = 0.005), anatomical stage (p<0.001) and assigned to higher stage (p = .001) were statistically significant variables. Hormone receptors and c-erb B2 receptor status are independent variables which impact OS and DFS in our patient group which is mostly consisted of early-stage cases according to anatomical stage. In prognostic staging, upstaging stands out as an independent prognostic factor for DFS. The 8th edition of AJCC prognostic stage groups determines the prognosis much better in our patient cohort.

123O Randomized phase II trial of neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in early HER2-positive breast cancer (ABCSG-52/ATHENE)

For most HER2-positive early breast cancer (EBC) patients (pts), neoadjuvant dual HER2 blockade with trastuzumab (T) and pertuzumab (P) plus poly-chemotherapy is standard of care. To improve the balance between toxicity burden and treatment outcomes, chemotherapy de-escalation has been a major focus in recent years. Among other immunogenic properties, anthracyclines can trigger an immunogenic cell death that engages the adaptive immune system. Within the ABCSG-52 trial we investigated a chemotherapy de-escalation immunotherapy regimen in HER2-positive EBC. Pts with previously untreated, histologically confirmed HER2-positive EBC (clinical prognostic stage cT1c-4a-d, N0–3,M0) were randomized 1:1 to two 3-weekly cycles of a chemotherapy-free induction phase (part 1) with TP plus 1200mg atezolizumab (TP+A) or TP alone. Afterwards, all pts received 4 cycles of TP+A in combination with epirubicin (part 2). The primary endpoint was pathological complete response (pCR; ypT0/Tis ypN0) in the overall study population. A pCR rate of ≥ 40% was considered as a positive trial result. Overall, 58 pts were randomized to TP-A (n=29) or TP (n=29) in 9 Austrian study centers. Median age was 57 (range 33-82), 16 pts (27.6%) had hormone-receptor (HR)-negative and 42 (72.4%) had HR-positive tumors. 45 pts (77.6%) had stage ≤ IIA and 13 (22.4%) ≥ IIB. In 35 pts a pCR was observed (60.3%; 95%CI 47.5% - 71.9%), 19 (65.5%) in the TP-A group and 16 (55.2%) in TP group (Δ 10.3%; 95%CI -14.7% - 35.4%). Residual cancer burden (RCB) class 0 or I was seen in 44 out of 55 pts (80%) with valid RCB assessment. Treatment emergent adverse events (AEs) grade ≥ 3 were reported in 17 pts (29.3%), 9 in TP-A group (31.0%) and 8 (27.6%) in TP group. No AEs of special interest (immune-related AEs, cardiac disorders grade ≥ 2, or infusion-related reactions) grade ≥ 3 were detected. Outcome according to PD-L1 expression status is currently analyzed and will also be presented at the meeting. For HER2-positive EBC, a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab and epirubicin is highly effective and safe and merits further investigation.

Abstract 1940: Outcomes of patients treated with neoadjuvant chemotherapy for breast cancer at a safety net hospital

Abstract Background: Neoadjuvant chemotherapy (NAC) is administered before surgery and expected to benefit certain breast cancer (BC) patients (pts). This study inspected outcomes of triple negative BC (TNBC), hormone receptor (HR) positive (+) HER2 negative (-), and HER2+ BC pts treated with NAC at John Peter Smith Hospital (JPS) in Tarrant County, TX. Methods: It is an IRB exempted retrospective review of JPS Oncology and Infusion Center’s registry data. Eligible pts were diagnosed with TNBC, HR+ HER2-, or HER2+ BC from 1/1/2016 to 12/31/2019 and underwent NAC. Age, race, NAC regimen, tumor grade, recurrence, and pt survival were collected from EPIC EMR. NCCN guidelines were used to standardize clinical prognostic and pathologic anatomic stages. Decrease in stage by at least one level was considered as improvement. Results: Refer to table for additional results. Total of 104 pts. 22 (21.2%) had recurrence, 14 (14.5%) had died. Using the full cox proportional hazard model, TNBC pts had a 3.214 times higher hazard of death/recurrence compared to other subsets (95% CI: 1.261, 8.193; p= 0.0145). 70 (67.3%) pts showed improvement in stage. 34 (32.7%) achieved pathological complete response (pCR). When compared to pts with residual disease, achieving pCR reduced hazard of death/recurrence by 71.6% (HR: 0.284; 95% CI: 0.095, 0.849; p= 0.0243). Conclusion: A clear unmet need is poor survival of Black TNBC pts. Safety net hospitals, like JPS, disproportionately treat Black pts. We show that attaining pCR correlates with improved survival, but less than a quarter of TNBC pts attained pCR. New NAC regimens with Pembrolizumab has become standard of care for TNBC pts since 2021 due to higher pCR rates. Still, there is a need for better NAC regimens to improve pCR in TNBC overall and clinical trials on new regimens should include Black pts. Also, more than a third of HR+ HER2- pts upstaged in LN after NAC. This suggests a need for pre-NAC radiology staging methods and better NAC regimen testing for this subset. TNBC(32 patients) HR+, HER2-(29 patients) HER2+(43 patients) TOTAL(104 patients, 103 women) Median Age Median Age 58 50 53 53 Racial Distribution of Patients Non-Hispanic White 9(28.1%) 11(37.9%) 11(25.6%) 31(29.8%) Black 18(56.3%) 12(41.4%) 15(34.9%) 45(43.3%) Hispanic 4(12.5%) 2(6.9%) 10(23.3%) 16(15.4%) Asian 1(3.1%) 4(13.8%) 7(16.3%) 12(11.5%) Clinical Prognostic Stage Before NAC and Surgery 1 1(3.1%) 0(0%) 9(20.9%) 10(9.6%) 2 8(25%) 13(44.8%) 20(46.5%) 30(28.8%) 3 22(68.8%) 16(55.2%) 14(32.6%) 52(50%) 4 1(3.1%) 0(0%) 0(0%) 1(0.9%) Pathologic Anatomic Stage After NAC and Surgery pCR 7(21.9%) 3(10.3%) 24(55.8%) 34(32.7%) 1 8(25%) 3(10.3%) 14(32.6%) 24(23.1%) 2 9(28.1%) 9(31%) 3(7%) 21(20.2%) 3 8(25%) 14(48.3%) 2(4.7%) 24(23.1%) 4 0(0%) 0(0%) 0(0%) 0(0%) Tumor Stage Difference Before/After Surgery Improvement 24(75%) 11(37.9%) 35(81.4%) 70(67.3%) Deterioration 1(3.1%) 7(24.1%) 0(0%) 8(7.7%) No Change 7(21.9%) 11(37.9%) 8(18.6%) 26(25%) Recurrence Recurrence 10(31.3%) 4(13.8%) 8(18.6%) 22(21.2%) Patients survived as of 9/19/2022 Survival 25(78.1%) 27(93.1%) 38(88.4%) 90(86.5%) Additional Significant Results Completion of NAC regimen 89 (85.6%) total pts Lymph Node (LN) Upstaging for HR+ HER2- 6 (20.7%) pts showed improvement in LN while 11 (37.9%) upstaged in LN pCR in Black TNBC pts Only 16% of Black pts achieved pCR Citation Format: Prakriti Srivastava, James-Michael Blackwell, Jolonda Bullock, Riyaz Basha, Kalyani Narra. Outcomes of patients treated with neoadjuvant chemotherapy for breast cancer at a safety net hospital [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1940.

Development of Brain Metastases Following Definitive Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> To describe the time course and likelihood of symptomatic presentation of brain metastases in the setting of locally advanced non-small cell lung cancer (LA-NSCLC) following definitive therapy. <h3>Materials/Methods</h3> Patients with LA-NSCLC treated with chemoradiation as definitive therapy between 2013-2020 (n = 219) were reviewed. Features including histologic subtype, T, N and clinical prognostic stage, presence of brain metastases and symptoms at time of presentation were recorded. Descriptive statistics were used to characterize the patient population, including incidence of brain metastases by histology, and the method of Kaplan and Meier was used to estimate brain metastasis free survival at 24 months. Fisher's exact tests were used to compare proportions between symptomatic and asymptomatic patients. <h3>Results</h3> A total of 219 patients met inclusion criteria. Histology including squamous cell carcinoma (SCC) (96), adenocarcinoma (88), and NSCLC-Not Otherwise Specified (NOS) (35). Median age was 67 years; 210 (96%) were current/former smokers, T stage was T0 (11.9%), T1 (21.9%), T2 (26.5%), T3 (18.3%), and T4 (21.5%). The majority of patients were N2 or N3 at treatment: N0 (5%), N1 (14.2%), N2 (60.7%), and N3 (20.1%). In total, 39 patients (17.8%) developed brain metastases. Incidence by histology varied with NSCLC-NOS showing the highest incidence (34.3%), followed by adenocarcinoma (23.9%), and SCC (6.2%). Brain metastasis free survival at 24 months was 72.9% (95% CI: 62.5-84.9%) for adenocarcinoma, 92.2% (95% CI: 86.3 – 98.5%) for SCC, and 53.3% (95% CI: 35.4 – 80.1%) for NSCLC-NOS. Median time to development of brain metastasis was 7.7 months (adenocarcinoma), 5.7 months (SCC), and 8.3 months (NSCLC-NOS). Overall, 85% of brain metastases occurred within 1 year. Ninety percent of patients were diagnosed with brain metastases after development of neurologic symptoms. Only 4 total patients had brain metastases discovered without symptoms. For patients presenting with symptomatic brain metastases, 91.4% required steroids versus 0% for those without symptoms (p <0.001). Symptomatic patients were more likely to require hospitalization at presentation, 65.7% vs 0% (p = 0.02). All asymptomatic patients with brain metastases were able to undergo stereotactic radiosurgery (SRS) alone, while only 40% of symptomatic patients received SRS monotherapy (p = 0.04). There was no statistically significant difference brain metastasis incidence based on treatment with adjuvant immunotherapy vs none for any histology (17.1% vs 18.1%, p = 1). <h3>Conclusion</h3> Brain metastases are a common source of morbidity and mortality in the setting of LA-NSCLC; however, there is no standard recommendation for surveillance brain imaging following therapy. Presentation with symptomatic brain metastases was significantly associated with need for more invasive management. This could strengthen an argument for the potential utility of surveillance brain imaging in the post-definitive setting.

Abstract 3686: Differences in disease presentation, and treatment outcomes of neoadjuvant chemotherapy for breast cancer among Hispanics in a minority-serving institution

Abstract Background: Response to neoadjuvant chemotherapy (NAC) for breast cancer varies by tumor characteristics and therapy regimen. Studies suggest that patient ethnicity is associated with differences in disease presentation, response to treatment, and outcomes. There exists a paucity of literature on the presentation and outcomes of NAC for breast cancer in Hispanic women. Methods: This is an IRB-approved retrospective study of breast cancer patients who underwent NAC at an NCI-designated Comprehensive Cancer Center from 2005-2020. We reviewed demographics, disease presentation, response to treatment, and outcomes. ER and PR status were categorized as low positive (1-9%), positive (≥ 10%) and negative. Treatment factors reviewed included completion of chemotherapy and type of surgery performed. Treatment response was noted as percent residual cellularity (0%, &amp;lt;10%, 10-30%, &amp;gt;30-80% and &amp;gt;80%) in the surgical specimen and pathologic stage. Outcomes were assessed as overall survival (OS) and recurrence. Results: 365 patients received neoadjuvant chemotherapy from 2005-2020, and 196 (53.7%) self-identified as Hispanic. Median follow-up was 13.65 years. Highest clinical stage at diagnosis was most frequently IIA (31.2%), followed by IIB (32.3%), with non-significant Hispanic ethnicity differences, although Hispanic patients presented with higher clinical prognostic stages: IIIA or higher (40.5% vs. 24.0%). Hispanics more frequently had grade 3 tumors (60% vs. 48%), ER low positive (10% vs. 7%) and ER negative (48% vs. 36%) (p=0.02). No significant differences were noted in triple negative disease or HER2 positive disease. Hispanics were diagnosed at younger average ages (48.9 vs. 53.0 years, p=0.001). No statistically significant differences were noted in time from diagnosis to NAC initiation, completion of chemotherapy, or surgical treatment received (lumpectomy vs. mastectomy, and sentinel node biopsy vs. dissection). Mastectomy was more likely for late-stage disease (OR=2.73, 95% CI: 1.66-4.49, p&amp;lt;0.001); Hispanic women with late-stage disease had 1.09-fold higher odds of receiving mastectomy, but this was non-significant (95% CI: 0.66-1.79). No significant ethnic differences were noted in pCR (p=0.69) or residual tumor cellularity (p=0.63). There was no significant association between residual cellularity and OS. OS rates were similar for Hispanic vs. Non-Hispanic women (HR: 1.15, 95% CI: 0.64-2.08, p=0.63). No difference was noted in ethnicity-based recurrence rates (21.4 vs. 20.1%). Conclusion: Self-identified Hispanic patients were diagnosed at a younger age, presented with higher ER negative and low-positive disease and worse prognostic clinical stage. However, given standard of care chemotherapy, there were no significant differences in their treatment response or outcomes compared to non-Hispanic patients. Citation Format: Sangeetha Prabhakaran, Christopher McNicoll, Vernon S. Pankratz, Nadja Falk, Jacklyn Nemunaitis, Jain Zhou, Payton A. Sandoval-Belt. Differences in disease presentation, and treatment outcomes of neoadjuvant chemotherapy for breast cancer among Hispanics in a minority-serving institution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3686.

The Effect of FDG-PET/CT on Clinical Prognostic Staging of Breast Cancer Patients being Planned Neoadjuvant Treatment.

To evaluate the effect of FDG-PET/CT in the radiological imaging of breast cancer (BC) patients planned for neoadjuvant treatment (NAT), on the clinical prognostic stage (CPS). A descriptive study. Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey, between June 2014 and September 2020. Consecutive patients with stage I-III breast cancer (BC) who were planned for neoadjuvant treatment (NAT). The distribution of CPS detected by both conventional radiological methods (c-CPS) and FDG-PET/CT (PET-CPS) were compared. Significant upstaging on CPS was detected with the addition of FDG-PET/CT to conventional imaging methods in 25/121 (20.7%) patients (p <0.001). In the c-CPS stage, IB, IIA, IIB, IIIA, IIIB patients, the stage change rate was 22.7%, 28.6%, 37.5%, 50%, and 9.1%, respectively. There was no change in patients with c-CPS stage IA and IIIC. There was a significant change in the cN stages (p <0.001), while no significant change was detected in the cT stages of the patients (p = 0.180). Upstaging was detected in 5/16 (6.3%, p=0.034), 14/71 (19.7%, p <0.01), 15 / 30 (50%, p <0.01) of initially cN 0, 1, 2 patients, respectively (p<0.001). The change in CPS was due to nodal upstaging. The effectiveness of including FDG-PET/CT in the initial radiological imaging in patients planned for NAT should be evaluated with prospective studies evaluating treatment choices to be used in NAT. Key Words: PET scan, Breast cancer, Positron emission tomography, Neoadjuvant treatment, Cancer staging, Staging system, TNM.

Tumor infiltrating lymphocyte stratification of prognostic staging of early-stage triple negative breast cancer

The importance of integrating biomarkers into the TNM staging has been emphasized in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging system. In a pooled analysis of 2148 TNBC-patients in the adjuvant setting, TILs are found to strongly up and downstage traditional pathological-staging in the Pathological and Clinical Prognostic Stage Groups from the AJJC 8th edition Cancer Staging System. This suggest that clinical and research studies on TNBC should take TILs into account in addition to stage, as for example patients with stage II TNBC and high TILs have a better outcome than patients with stage I and low TILs.

Re: Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-specific Mortality Results from the International Staging Collaboration for Cancer of the Prostate

Re: Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-specific Mortality Results from the International Staging Collaboration for Cancer of the Prostate

The combination phenotype of B-cell specific Moloney murine leukaemia virus integration site 1 (BMI1) and CD44+/CD24−/low associates with poor clinicopathological features in African patients with breast cancer

Cancer stem cell theory has revolutionalised breast cancer (BC) treatment and prognosis. The role of B cell specific Moloney murine leukaemia virus integration site 1 (BMI1) cancer stem cell marker in BC is not entirely understood. Herein, we have studied the association between BMI1, its combination phenotypes with other breast cancer stem cells and BC behaviour in a cohort of African patients.Tissue microarray of BC cohort (n = 222) from Ghanaian patients was immunohistochemically stained for BMI1. The associations between BMI1, clinicopathological features, other cancer stems cell markers and outcome were analysed using Pearson's chi-square, and Kaplan Meier's log rank-test.High expression of BMI1 was observed in 85% of cases. CD44+/CD24−/low/BMI1+ phenotype was associated with unfavourable clinicopathological features including higher tumour grade (p = 0.013), larger tumour size (p = 0.048), and high clinical prognostic stage (p = 0.018). However, the CD44+CD24−/lowBMI1− was the only phenotype that showed improved BCSS.BMI1 may contribute to the inherent tumour aggressiveness of African BC. Additional functional studies are warranted to identify the underlying mechanisms and the role of stem cell network in BC development and behaviour.

A simplified breast cancer prognostic score: comparison with the AJCC clinical prognostic staging system

There have been many breast cancer prognostic models proposed in the last few decades, varying in their methods of development and validation, predictors, outcomes, and patients included. Most models were developed to assess prognostic outcomes for early breast cancers. In this study, we established a simplified prognostic score to predict survival outcomes in all breast cancer patients. A total of 36,152 breast cancer patients diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were used as the training dataset. Multivariate analyses were performed to identify independent factors for disease-specific survival (DSS). A prognostic score was calculated by summing the point values based on the magnitude of the hazard ratio for all independent factors. The authors institutional cohort (n = 4982) was used as the validation dataset. The prognostic score model consisting of histologic grade, ER, PR, HER2, and TNM status demonstrated a similar predictive power when compared to the revised 8th AJCC Clinical Prognostic Staging system in both training and validation datasets, whereas the addition of age and race did not facilitate stratification of prognostic groups. Pairwise comparison of hazard ratios showed a significant difference in all categories when compared to their proximate groups in both prognostic schemes in the SEER database, while the prognostic score model demonstrated a slightly better discriminating power in the validation dataset. Thus, the proposed prognostic score showed at least a comparable predicting power for survival outcomes in breast cancer patients receiving standard-of-care treatment when compared to the AJCC Clinical Prognostic Stage. This prognostic model provides a convenient and alternative modality in clinical practice thus warranting further validation using larger cohorts with longer follow-up.

Impact of the COVID-19 Pandemic on Breast Cancer Stage at Diagnosis, Presentation, and Patient Management.

IntroductionThe COVID-19 pandemic caused delays in breast cancer management forcing clinicians to potentially alter treatment recommendations. This study compared breast cancer stage at diagnosis and rates of neoadjuvant therapy among women presenting to our institution before and during COVID-19.MethodsRetrospective chart review of patients with a new breast cancer diagnosis from March 2020–August 2020 (during-COVID-19) were compared with March 2019–August 2019 (pre-COVID-19). We compared stage at diagnosis, clinical/demographic features, and neoadjuvant therapy use between the time periods.ResultsA total of 573 patients included: 376 pre-COVID-19, 197 during-COVID-19. Method of cancer detection was by imaging in 66% versus 63% and by physical findings/symptoms in 34% versus 37% of patients comparing pre-COVID-19 to during-COVID-19, p = 0.47. Overall clinical prognostic stage did not differ significantly (p = 0.39) between the time periods, nor did cM1 disease (2% in each period); 23% pre-COVID-19 and 27% during-COVID-19 presented with cN+ disease (p = 0.38).Neoadjuvant therapy use was significantly higher during-COVID-19 (39%) versus pre-COVID-19 (29%, p = 0.02) driven by increased neoadjuvant endocrine therapy (NET) use (7% to 16%, p = 0.002), whereas neoadjuvant chemotherapy use did not change (22% vs. 23%, p = 0.72). In HR+/HER2− disease, NET use increased from 10% pre-COVID-19 to 23% during-COVID-19 (p = 0.001) with a significant increase in stage I patients (7 to 22%, p < 0.001) and nonsignificant increases in stage II (18 to 23%, p = 0.63) and stage III (9 to 29%, p = 0.29).ConclusionsBreast cancer stage at diagnosis did not differ significantly during-COVID-19 compared with pre-COVID-19. More patients during-COVID-19 were treated with NET, which was significantly increased in stage I HR+/HER2− disease.

Clinical Prognostic Factors for Patients With Esophageal Cancer Treated With Definitive Chemoradiotherapy.

BackgroundTreatment with definitive chemoradiotherapy (CRT) is the best option for patients with locally advanced esophageal tumors considered unresectable or for patients without clinical conditions to undergo surgical treatment. Technological advances in radiotherapy in the last decades have made treatment more accurate with less toxicity, and the association with more effective systemic treatment has been gradually improving survival rates.AimEvaluate clinical prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with esophageal cancer treated with definitive radiotherapy (RT) and chemotherapy (ChT).Material and methodsThe clinical records of 60 patients treated from April 2011 until December 2019 with esophageal cancer considered unresectable and/or without clinical conditions for surgery, treated with definitive CRT, were analyzed. All patients had upper digestive endoscopy (UDE) with positive biopsy, neck, chest, and abdominal CT scan, and 18F-fluorodeoxyglucose positron-emission tomography (PET-CT). Patients were followed with physical examination and CTs every three months in the first and second years and every six months from the third year of follow-up. UDE was made every three to six months after the end of the treatment or in suspicion of tumor recurrence. PET-CT was also performed in the follow-up when clinically necessary. Local and regional failure (LRF) was defined as abnormalities in the image tests within the planning target volume (PTV) and/or positive biopsy on UDE. Any other failure was defined as a distant failure (DF). PFS was defined in the record of the first tumor recurrence site and OS in the death record from the date of the start of treatment.ResultsThe median age of the patients was 66 years (range: 33 to 83 years) and 46 patients (76.7%) were male. Squamous cell carcinoma (SCC) was the most frequent histological type (85%). Most patients had tumors located in the mid-thoracic esophagus (53.3%) and stage III or IV (59.9%). All patients were treated using 3D (76.7%) or intensity-modulated radiotherapy (IMRT; 23.3%). The median total dose was 50.4Gy (41.4-50.4). All patients received platinum-based ChT concomitant with RT. The most common regimen used was carboplatin and paclitaxel, with a median of five cycles. With a median follow-up of 19 months, the median PFS and OS were 10 and 20 months, respectively. LRF and DF as the first site of failure were observed in 22 (36.6%) and 26 (43.3%) patients, respectively. In the univariate analysis, tumor length lower than 2.6 cm, gross tumor volume (GTV) volume lower than 28 cm3, clinical tumor stages T1 and T2, clinical node stage N0, clinical prognostic stage groups I and II, and complete response to treatment, were statistically significant factors for better PFS and OS. In the multivariate analysis, the presence of clinical nodal stage N0 was related to better PFS (p=0.02).ConclusionNode clinical status was the most important clinical factor for PFS. Despite all the technical progress observed in radiotherapy, treatments concomitant with platinum-based chemotherapy are associated with high levels of LRF and DF. New strategies in systemic therapy and radiotherapy are necessary for improving outcomes.

Biochemical and Molecular Diagnostic Indicators for Cancer

Biomarkers are substances that are either secreted by the tumor or produced by the body in response to the presence of cancer. Biomarkers serve as an objective measure for evaluation of normal and pathological processes as well as pharmacological responses to a therapeutic intervention. Cancer studies are usually difficult to interpret, especially based on the contemporary medical diagnosis. In this circumstance, biomarkers are developing as reliable diagnostic metabolites, which have many promising applications in oncological screening, differential diagnosis, risk assessment, response to treatment, and examining the progression of disease. Genome or protein based prognostic biomarkers are available, for numerous cancer types, for potential inclusion into clinical prognostic staging methods. However, there lies difficulty in translating these biomarkers into clinical outcomes. This review concerns important biomarkers related to wide varieties of cancer and also elucidates mode of action of few major biomarkers.

Relationship between Prognostic Stage in Breast Cancer and Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

This retrospective study examined the relationship between the standardized uptake value max (SUVmax) of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and the prognostic stage of breast cancer. We examined 358 breast cancers in 334 patients who underwent 18F-FDG PET/CT for initial staging between January 2016 and December 2019. We extracted data including SUVmax of 18F-FDG PET and pathological biomarkers, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and nuclear grade. Anatomical and prognostic stages were determined per the American Joint Committee on Cancer (eighth edition). We examined whether there were statistical differences in SUVmax between each prognostic stage. The mean SUVmax values for clinical prognostic stages were as follow: stage 0, 2.2 ± 1.4; stage IA, 2.6 ± 2.1; stage IB, 4.2 ± 3.5; stage IIA, 5.2 ± 2.8; stage IIB, 7.7 ± 6.7; and stage III + IV, 7.0 ± 4.5. The SUVmax values for pathological prognostic stages were as follows: stage 0, 2.2 ± 1.4; stage IA, 2.8 ± 2.2; stage IB, 5.4 ± 3.6; stage IIA, 6.3 ± 3.1; stage IIB, 9.2 ± 7.5, and stage III + IV, 6.2 ± 5.2. There were significant differences in mean SUVmax between clinical prognostic stage 0 and ≥II (p < 0.001) and I and ≥II (p < 0.001). There were also significant differences in mean SUVmax between pathological prognostic stage 0 and ≥II (p < 0.001) and I and ≥II (p < 0.001). In conclusion, mean SUVmax increased with all stages up to prognostic stage IIB, and there were significant differences between several stages. The SUVmax of 18F-FDG PET/CT may contribute to prognostic stage stratification, particularly in early cases of breast cancers.

Refining breast cancer prognosis by incorporating age at diagnosis into clinical prognostic staging: introduction of a novel online calculator.

American Joint Committee on Cancer (AJCC) clinical staging is used to estimate breast cancer prognosis, but individual patient survival within each stage varies considerably by age at diagnosis. We hypothesized that the addition of age at diagnosis to the staging schema will enable more refined risk stratification. We performed a retrospective population analysis of adult women diagnosed with invasive breast cancer between 2010 and 2015 registered in SEER. Multivariable Cox hazards models were used to evaluate the association of AJCC 8th edition clinical prognostic stage (CPS) and age with risk of overall mortality. Separate hierarchical models were fit to the data: Model 1: CPS alone; Model 2: CPS + age + age2; and Model 3: CPS + age + age2 + CPS x age + CPS x age2. Models were compared by the Akaike information criterion (AIC), the c-statistic for time-dependent receiver operator characteristic curves, and category-free net reclassification improvement (NRI). Internal validation was performed using bootstrapping samples. Among 86,637 women, the median follow-up was 36months and 3-year overall survival was 91.9% ± 0.1%. Age significantly modified the effect of CPS on survival (p < 0.0001). Model 3 was the most precise, with the lowest AIC (126,619.63), the highest c-statistic (0.8212, standard error 0.0187), and superior NRI indices. Age at diagnosis is a highly prognostic variable that warrants consideration for inclusion in future editions of the AJCC Breast Cancer Staging Manual.

Abstract PS6-23: Comparison between the American joint committee on cancer (AJCC) anatomic and prognostic stages for breast cancer

Abstract Introduction: The knowledge regarding the tumor biology of breast cancer has grown substantially and resulted in the identification of different breast cancer subtypes based on their molecular profile, which led to an important change in treatment, it went from standardized therapy for personalized therapy. A panel of experts and representatives from AJCC were responsible for preparing the newest Cancer Staging Manual. The panel recognized the clinical usefulness of biological factors such as histological grade, expression of hormone receptors - HR (estrogen and progesterone) and overexpression and / or amplification of the human epidermal growth factor 2 (HER2) receptor in predicting patient survival and incorporated data regarding these biomarkers in the new staging system. In addition, for eligible cases, the ‘Recurrence score’ was also incorporated, a score generated by the analysis of OncotypeDx (genomic test). The new manual, therefore, started to use 3 stays. Anatomical staging - based on the classic TNM; the clinical prognostic staging and pathological prognosis staging - TNM association with the prognostic biomarkers (using clinical data in the first and data after surgical treatment in the second). Objective: To verify the concordance between anatomical staging from the 7th edition of the AJCC manual and the prognosis from its 8th edition in a cohort of patients with breast cancer at the Hospital do Servidor Público Estadual de São Paulo. Methodology: Observational and cross-sectional study, which evaluated patients undergoing surgical treatment at Hospital do Servidor Público Estadual from March 2014 to March 2019. Information was collected regarding age, menopausal status, tumor characteristics, anatomical and clinical staging, neoadjuvant chemotherapy, adjuvant chemotherapy and radiotherapy and type of surgery performed. The patients were staged using the digital platform “TNM8 Breast Cancer Calculator”. Results: 805 patients were included in the analysis. All patients were female, aged between 29 and 97 years, mostly in the post-menopausal period (78.88%). 74.04% of the cases were positive for ER, 66.21% positive PR and 88.07% HER2 negative. Prognostic staging downgraded a total of 285 out of 805 patients (35.4%). Almost all of the cases that decreased in staging were ER and / or PR + (283 of 285). Most of those who went up were Triple Negatives (100 out of 111). Conclusion: Prognostic Staging changes staging in almost half of the cases and there was a greater number of staging decreases in total and an association of increased staging with tumors considered to have a worse prognosis, which is in agreement with several studies already carried out since the launch of the new manual. Table 1. Changes in the staging groups. Anatomical Staging vs. Prognostic StagingAnatomical Staging (%)StageIAIBIIAIIBIIIAIIIBIIICIVPrognostic Staging (%)IA2486972Total that decreased staging285 (35,4%)IB21472619IIA602727IIB22294IIIA34297IIIB17122014IIIC14226IV4Total staging that increased 111(13,8%)Total unchanged 409 (50,8%) Table 2. Relationship of the immunohistochemical profile and change of stagingBiomarkersTotal (%)DifferenceTotalHR + / HER2 -575 (71,42%)-196 (16,70%)-2140 (24,34%)-321 (3,65%)0308 (53,57%)+110 (1,74%)HR + / HER2 +49 (6,09%)-19 (18,37%)-217 (34,69%)022 (44,90%)+11 (2,04%)HR - / HER2 +47 (5,84%)-12 (4,3%)045 (95,7%)HR - / HER2 -134 (16,65%)034 (25,4%)+169 (51,5%)+231 (23,1%)805 (100%) Citation Format: Mariana Soares Cardoso, Marcelo Antonini, Odair Ferraro, Matheus de Paula Solino, Samira Marcondes Cabral, Raissa Naiara Alves de Barros Vasconcelos. Comparison between the American joint committee on cancer (AJCC) anatomic and prognostic stages for breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-23.

The role of ALDH1A1 in contributing to breast tumour aggressiveness: A study conducted in an African population

Aldehyde dehydrogenase 1 member A1 (ALDH1A1) is one of the most well studied breast cancer stem cells. Its expression has been associated with poor clinicopathological features and clinical outcomes in several studies. This paper studies the expression of ALDH1A1 and its combination with CD44+/CD24−/low breast cancer stem cell and their association with clinicopathological parameters and molecular subtypes. MethodTissue Microarray was constructed from 222 Formalin Fixed Paraffin Embedded (FFPE) breast cancer tissues. The expression of ALDH1A1, CD44 and CD24 were assessed by Immunohistochemistry (IHC). The association of ALDH1A1 and its association with clinicopathological parameters, molecular subtypes, CD44 and CD24 were studied in an African population. The association between CD44+/CD24−/low/ALDH1+ and the clinicopathological phenotypes were also studied. ResultsA high ALDH1A1 expression of 90% was recorded in this study. No association was found between ALDH1A1 and clinicopathological parameters. ALDH1A1 was positively associated with CD24 (r = 0.228, OR-4.599 95% CI- 1.751–12.076, p = 0.001) and CD44 (r = 0.228, OR-5.538 95%CI- 1.841–16.662, p = 0.001) but not associated with CD44+/CD24−/low (r = 0.134, OR- 2.720 95%CI- 0.959–7.710, p = 0.052). CD44+/CD24−/ALDH1+ however had significant associations with Age (p- 0.020, r = 0.161, OR- 2.771, 95%CI 1.147–6.697), Gender (p = 0.004, OR- 15.333 95%CI 1.339–175.54), Tumour grade (p = 0.005, r = 0.197, OR-3.913 95%CI 1.421–10.776) and clinical prognostic staging (p = 0.014, r = 0.182, OR-3.028 95%CI- 1.217–7.536). There was no association between CD44+/CD24−/ALDH1+ and the molecular subtypes. ConclusionThe high expression of ALDH1A1 in breast cancer makes it an important target for targeted therapy. This study further confirms the increased tumourigenicity of CD44+/CD24−/ALDH1+ combination phenotype and its association with increased tumour grade and clinical prognostic stage. Survival studies of ALDH1A1 and other breast cancer stem cells in African populations are strongly recommended to help further understand their effect on tumour aggressiveness.

Discontinuous Involvement of Spermatic Cord Soft Tissue in Testicular Germ Cell Tumors: A Multi-Institution Experience

Abstract Introduction/Objective In the 8th Edition AJCC Cancer Staging Manual, discontinuous involvement of spermatic cord soft tissue (DISC) by testicular germ cell tumors (GCT) is regarded as metastatic deposit (pM1), placing the patient in clinical prognostic stage group (CPSG) III. We conducted a multi-institution study to corroborate or refute the current recommendations. Methods: Thirty-eight cases of GCT with spermatic cord involvement were collected from 13 institutions in Europe, Phillipines and America. Clinical and pathologic data was obtained. Results Tumors included 28 (73%) non-seminomatous and 10 (26%) seminomatous GCTs. Mean testicular tumor size was 6.6 cm (range 1.3-18). After review by an uropathologist, cases were classified as cord LVI [T2] (n=3), continuous cord involvement (CCI) [T3] (n=13), and DISC (n=22). Mean cord tumor size for DISC was 0.9 cm (range 0.1-4.5). CPSG was available for 33 and follow-up (FU) for22 patients with a mean length of FU of 38 months (range 2-144). Seven (39%) DISC patients were CPSG II (regional LN metastases), and 11 (61%) CPSG III (distant metastases). On FU, 5 (45%) DISC patients had no evidence of disease (NED); 6 (55%) were alive with disease (AWD). Three (25%) CCI patients were CPSG I (local disease), 6 (50%) CPSG II, and 3 (25%) CPSG III. On FU, 6 (60%) CCI patients were NED, 4 (40%) AWD. Cord LVI patients were one in each CPSG. One cord LVI patient was NED, the others were lost at FU. All DISC (100%) patients with available CPSG had advanced disease (CPSG II or III), compared to 75% of CCI, and 67% of cord LVI patients. Conclusion Although it did not reach statistical significance (p=0.054; Fisher’s exact test), DISC patients were more likely to have CPSG II and III compared to CCI patients. Our findings suggest a worse behavior in patients with DISC, supporting a higher pathologic stage than CCI.