Adjuvant Therapy Decisions Research Articles

Satisfaction and Regret With Decision Making in Older Women With Breast Cancer

<h3>Purpose/Objective(s)</h3> Shared decision making is a fundamental component of the conversation between physicians and older women with early-stage breast cancer making decisions to omit radiation therapy. The purpose of this study is to report patient comfort and satisfaction levels with decision making. <h3>Materials/Methods</h3> Women with pre-invasive or early-stage breast cancer who had been given the option to omit radiation therapy were identified. Two validated instruments (decisional regret and satisfaction with decision) were provided to all women with 5 choices (strongly agree, agree, neither agree nor disagree, disagree, strongly disagree). All women then underwent a qualitative interview about their decision making process, and were given option of $50.00 gift card after completion. Interviews were transcribed, and common themes were coded using qualitative data analysis software by two members of the research team. <h3>Results</h3> Thirty-six women diagnosed with early stage or pre-invasive breast cancer from 2013-2020 were consented. Median age at diagnosis was 72. Twenty (55%) chose to omit RT. Majority of women (92%) agreed or strongly agreed that it was the right decision, and that they were satisfied about being adequately informed about the issues that were important to the decision making process. In women who had chosen radiation therapy, one woman expressed regret regarding side effects of radiation therapy: "So with the surgery and the shrinking, then I think I would have been better off if I had gone with a mastectomy and probably a double and then had reconstruction." Other women expressed regret with radiation in the context of coordinating the complexities of treatment: "I might have decided to just have a double mastectomy. I wouldn't had to have the cancer drug. I wouldn't have had the radiation. It was just much more complicated than I thought in my mind," and "then again, in my head, there's something about putting radiation into my body when there's another option where one is putting something in and the pill is taking something out." While no women expressed regret regarding omission of radiation (pre- and post-COVID-19 pandemic), some women expressed knowledge deficit or poor expectation of the side effects of hormonal blockade: "We really didn't talk about the side effects. I've gotten more information from my friends that are on the pill than I have from the doctor. Doctor's attitude was you need to take this, and you're going to take it, and we're going to monitor you," [the medical oncologist] said I shouldn't have any problem." <h3>Conclusion</h3> Older women with early-stage breast cancer offered options for omission of radiation therapy did not express regret regarding their decision to omit radiation, but sometimes felt that they were not informed about the expectations and side effects of hormonal blockade. Additional educational tools to assist in adjuvant therapy decision making regarding radiation therapy and endocrine therapy options are warranted.

Omission of sentinel node biopsy for breast cancer: Historical context and future perspectives on a modern controversy.

For older patients with clinically lymph node-negative breast cancer who have estrogen receptor-positive tumors and are treated with tamoxifen, randomized trials comparing axillary lymph node dissection (ALND) versus no ALND show that the omission of ALND improves patient quality of life and has no adverse effects on mortality. These results have served to justify sentinel node biopsy (SNB) omission in selected older patients with breast cancer. More recently, clinical trials were launched to assess SNB omission in younger patients, with recurrence and survival as the primary outcomes of interest. Three important considerations serve as the basis for these ongoing trials. First, it is assumed that SNB omission will improve patient quality of life, although, to date, there is no level I evidence to support this assumption. Second, axillary surgery has never been shown to reduce breast cancer mortality, but it does reduce the risk of axillary recurrences, although adjuvant systemic therapy and radiotherapy also reduce these recurrence risks. Finally, nodal status is losing importance as a guide for adjuvant systemic therapy decision making because these decisions are now increasingly predicated on tumor biomarkers and gene profiling, but it is gaining importance for adjuvant radiotherapy decision making. Because quality-of-life considerations are the primary motivation for abandoning SNB, there is a need for randomized trials comparing SNB versus no SNB/no axillary surgery, with quality of life as the primary end point (level I evidence). Moreover, suitable alternatives to guide adjuvant radiotherapy decision making will require validation before SNB omission can be justified for patients of all ages who have clinically node-negative breast cancer. LAY SUMMARY: In this review article, the authors provide a brief historical overview of the role of axillary surgery in breast cancer management and discuss additional studies and ramifications that should be considered before abandoning the sentinel node biopsy (SNB) procedure. Specifically, there is a need for level I evidence demonstrating that omission of the SNB procedure will improve patient quality of life and a need to validate suitable alternatives to SNB as a guide for adjuvant radiotherapy decision making.

The management of HER2‐positive early breast cancer: Current and future therapies

Advances in human epidermal growth factor receptor 2 (HER2)-directed therapies have revolutionised the care of patients with HER2-positive breast cancer. While adjuvant trastuzumab in combination with chemotherapy has dramatically improved the prognosis for patients with early-stage disease, up to a quarter of patients will develop recurrent disease. The standard-of-care treatment paradigm has evolved with the introduction of newer HER2-directed therapies and increasing use of neoadjuvant systemic therapy, the latter providing us with important functional data to HER2-directed therapies and impacting subsequent adjuvant therapy decisions. However, these new strategies come at a cost of increased toxicity and economic burden, and only a subset of patients benefit from such approaches. Thus, ongoing work is required to identify predictive biomarkers of response, to de-escalate treatment in patients who may do just as well with less therapy, and new therapeutic approaches for patients who do not respond to currently used therapies. In this review, we will examine the current therapeutic landscape, summarise the latest evidence, and list the current treatment algorithms for early stage HER2-positive breast cancer.

Sentinel lymph node procedures in endometrial cancer: an international multicenter experience

Objectives: Lymphadenectomy as part of surgical staging for endometrial cancer can define risk of recurrence and guide clinical decision-making for adjuvant therapy. While sentinel lymph node (SLN) mapping significantly reduces surgical complications and conserves an element of staging, its clinical significance remains controversial. The purpose of this study was to evaluate the incidence of SLN metastases and to identify risk factors and outcomes associated with positive SLNs. Methods: An international population-based retrospective review in three tertiary care academic centers was conducted on patients with endometrial cancer undergoing SLN biopsy as part of surgical staging for apparent early stage endometrial cancer. Multivariate logistic regression was performed to assess predictors of SLN positivity and to estimate the effect of SLN metastases on overall survival (OS) and progression-free survival (PFS). Results: One thousand and twelve patients were included with an average age of 60 years (24-90). The majority of women had Stage IA (68.9%) and low-grade histology (76.9%). Indocyanine green was used to identify SLNs in 535 (52.9%) women with an overall uptake at the whole-patient level of 94.0%. The overall incidence of SLN metastases was 5.7% (n=58). Cancer Antigen 125 > 35U/mL (OR=3.8 95% CI: 1.4-10.5; p=0.013) and presence of lymphovascular space invasion (OR=15.8, 95% CI: 5.6-44.7; p Conclusions: This is the largest international multicentered study evaluating SLN identification in endometrial cancer. Cancer Antigen 125 was identified as a preoperative independent risk factor associated with SLN positivity and can be used to optimize patient selection and surgical planning. Our data support the current literature suggesting that SLN biopsy for endometrial cancer should become standard of care. The procedure is associated with minimal morbidity and mortality, and has excellent performance.

Surgeon practice patterns in transoral robotic surgery for HPV-related oropharyngeal cancer

ObjectivesAnalyze how otolaryngologists approach HPV-related oropharyngeal cancer in terms of patient selection for transoral surgery, perceptions of treatment related risks and benefits, and adjuvant treatment decisions. Materials and MethodsA survey on HPV-related cancer management was distributed to otolaryngologists in the US through RedCap. Differences in responses were analyzed using Pearson’s chi-squared and Fisher’s exact tests. ResultsA total of 111 out of 143 (77.6%) otolaryngologists completed the survey. Overall, most prefer treating T1/T2 tumors using transoral robotic surgery (TORS) and T3 tumors through primary radiation therapy (RT), though there were significant differences between cohorts. Non-fellowship-trained surgeons and those in community practices favored RT for T1/T2 more than their fellowship-trained and academic counterparts, respectively. For adjuvant treatment, non-fellowship-trained surgeons favored adjuvant CRT, whereas fellowship-trained surgeons preferred only adjuvant RT, for patients with lymphovascular or perineural invasion, >1 lymph node involvement, or close deep margins. TORS was viewed as having less adverse sequelae (i.e. dysphagia, dysphonia, xerostomia). Though the two modalities had similar oncologic outcomes, TORS was perceived as providing better quality of life (QOL). ConclusionsThere are variations in HPV-related OPSCC management based on surgeon background and preferences across the US. TORS and primary RT are believed to offer similar oncologic control, but the former provides lesser adverse sequelae and better QOL. Additionally, surgeon demographics (i.e. fellowship status, practice type, and region) can affect management decisions, including patient selection for TORS and adjuvant therapy decisions. Further study is required to better understand and standardize appropriate HPV-positive OPSCC management.

Prediction of recurrence after surgery in colorectal cancer patients using radiomics from diagnostic contrast-enhanced computed tomography: a two-center study.

To assess the value of contrast-enhanced (CE) diagnostic CT scans characterized through radiomics as predictors of recurrence for patients with stage II and III colorectal cancer in a two-center context. This study included 193 patients diagnosed with stage II and III colorectal adenocarcinoma from 1 July 2008 to 15 March 2017 in two different French University Hospitals. To compensate for the variability in two-center data, a statistical harmonization method Bootstrapped ComBat (B-ComBat) was used. Models predicting disease-free survival (DFS) were built using 3 different machine learning (ML): (1) multivariate regression (MR) with 10-fold cross-validation after feature selection based on least absolute shrinkage and selection operator (LASSO), (2) random forest (RF), and (3) support vector machine (SVM), both with embedded feature selection. The performance for both balanced and 95% sensitivity models was systematically higher after our proposed B-ComBat harmonization compared to the use of the original untransformed data. The most clinically relevant performance was achieved by the multivariate regression model combining a clinical variable (postoperative chemotherapy) with two radiomics shape descriptors (compactness and least axis length) with a BAcc of 0.78 and an MCC of 0.6 associated with a required sensitivity of 95%. The resulting stratification in terms of DFS was significant (p = 0.00021), especially compared to the use of unharmonized original data (p = 0.17). Radiomics models derived from contrast-enhanced CT could be trained and validated in a two-center cohort with a good predictive performance of recurrence in stage II et III colorectal cancer patients. • Adjuvant therapy decision in colorectal cancer can be a challenge in medical oncology. • Radiomics models, derived from diagnostic CT, trained and validated in a two-center cohort, could predict recurrence in stage II and III colorectal cancer patients. • Identifying patients with a low risk of recurrence, these models could facilitate treatment optimization and avoid unnecessary treatment.

Neoadjuvant Chemotherapy for Breast Cancer: Moving Beyond Pathological Complete Response in the Molecular Age.

This review focuses on neoadjuvant chemotherapy for breast cancer which introduces practical issues for pathologists, including predicting response, optimising specimen handling, size measurement and assessment of residual disease, and recent advances in management of the axilla. The role of neoadjuvant chemotherapy in breast cancer is increasing, and it has become standard of care for high risk Human Epidermal Growth Factor Receptor 2 positive and triple negative breast cancers. The benefits of the neoadjuvant approach extend beyond pathological complete response to tumour downstaging permitting conservative surgical options in the breast and axilla, and assessment of response provides valuable prognostic information to enable escalation and de-escalation of adjuvant therapy to optimise oncological outcomes. Hence histopathologists play a vital role in patient management in the neoadjuvant setting. Optimal patient selection for neoadjuvant chemotherapy requires consideration of pre-treatment histopathological and molecular tumour characteristics. Post chemotherapy, tumour staging can be challenging, and changes in criteria for measurement of primary tumour and metastases in the 7th and 8th editions of the TNM have led to confusion amongst pathologists. This review offers practical guidance on specimen handling and measurement of lesion size. Moving forwards more detailed information on degree of response will be required for adjuvant therapy decision making, and the Residual Cancer Burden is emerging as the preferred method for quantifying residual disease not just within clinical trials but in routine practice. Recent advances in management of the axilla are discussed, including the significance of minimal residual disease in the form of isolated tumour cells and micrometastases which portend a worse prognosis in the neoadjuvant setting. CONCLUSION: Neoadjuvant chemotherapy now forms part of routine breast cancer management, and detailed histopathological assessment and an understanding of the importance of molecular tumour biology is essential for clinical decision making.

Impact of pathological response after neoadjuvant chemotherapy on adjuvant therapy decisions and patient outcomes in gastrointestinal cancers.

BackgroundNeoadjuvant chemotherapy (NAC) is frequently used in gastrointestinal cancers (GIC), and pathological, radiological, and tumor marker responses are assessed during and after NAC.AimTo evaluate the relationship between pathologic, radiologic, tumor marker responses and recurrence‐free survival (RFS), overall survival (OS), adjuvant chemotherapy (AC) decisions, and the impact of changing to a different AC regimen after poor response to NAC.Methods and resultsMedical records of GIC patients treated with NAC at Mount Sinai between 1/2012 and 12/2018 were reviewed. One hundred fifty‐six patients (58.3% male, mean age 63 years) were identified. Primary tumor sites were: 43 (27.7%) pancreas, 62 (39.7%) gastroesophageal, and 51 (32.7%) colorectal. After NAC, 31 (19.9%) patients had favorable pathologic response (FPR; defined as College of American Pathologists [CAP] score 0–1). Of 107 patients with radiological data, 59 (55.1%) had an objective response, and of 113 patients with tumor marker data, 61 (54.0%) had a ≥50% reduction post NAC. FPR, but not radiographic or serological responses, was associated with improved RFS (HR 0.28; 95% CI 0.11–0.72) and OS (HR 0.13; 95% CI 0.2–0.94). Changing to a different AC regimen from initial NAC, among all patients and specifically among those with unfavorable pathological response (UPR; defined as CAP score 2–3) after NAC, was not associated with improved RFS or OS.ConclusionsGIC patients with FPR after NAC experienced significant improvements in RFS and OS. Patients with UPR did not benefit from changing AC. Prospective studies to better understand the role of pathological response in AC decisions and outcomes in GIC patients are needed.

Does multiplicity of synchronous multiple lung primaries (SMLPs) affect prognosis.

e20530 Background: SMLPs are detected more commonly due to advancements in screening technology. Their workup and classification; however, are still lacking a clear standard. T stage of the largest lesion has been used as the major prognostic marker. This; however, does not take the number of SMLPs and their genomic drivers into consideration. This study aims to identify and review common risk factors associated with SMLPs and determine whether the number of primaries influence the prognosis. Methods: A systematic review of the literature published between 2000 and 2021 was conducted through PubMed and Medline by using the combination of keywords, including: “synchronous multiple primary lung cancer”, “simultaneous multifocal lung cancer”, “synchronous solitary lung metastasis”, “risk factor” and “prognosis”. A total of fifty studies were identified, among them only sixteen retrospective research articles and two review articles were relevant to the study at hand. Results: Sixteen retrospective studies including a total of 1685 eligible patients were reviewed. Thirteen of these studies reported the main histology type to be adenocarcinoma with a ratio ranging from 35% to 96.8%. Eight studies have reported the numbers of synchronous primary lung cancers, including one study found 11 SMLPs. Among these, one study by van Rens found number of SMLPs impact prognosis adversely compared to a single lung cancer. However, three other studies demonstrated multiple SMPLs do not adversely affect survival (Finley et al, 2010; Kocaturk et al, 2011; Li et al, 2020). Four of the sixteen studies analysed the effect of multiple lobes involvement and distance between tumors, with varying conclusions; two studies reported no difference in prognosis while one study revealed worse survival with multiple lobe involvement and one study found favorable outcome. Most studies confirm the usual prognostic factors for SMLPs, including: gender, smoking, type of surgery, comorbidities and adjuvant therapy. The median 5 year OS reported for SMLPs is 66%, with a wide range from 19% to 95.8%.The 3 year OS is 75% in most studies. Conclusions: The data on how the number of SMLPs affects the prognosis is uncertain. The current recommendation to base the decision for adjuvant therapy on the highest T stage is not supported by prospective evidence or consistent among published case series. Considering the recent approval of targeted therapies in early stage lung cancers, a better prognostic scoring system for SMLPs is required.

Circulating tumor DNA as markers of dynamic recurrence risk and adjuvant chemotherapy benefit in resected non-small cell lung cancer.

3028 Background: A significant proportion of non-small cell lung cancer (NSCLC) patients relapse after surgical resection with or without adjuvant therapy. The detection of molecular residual disease (MRD) has great potentials to stratify postoperative risk and facilitate early recurrence diagnosis. Here, we aim to evaluate the clinical utility of serial plasma circulating tumor DNA (ctDNA) in MRD detection, adjuvant therapy guidance, and recurrence risk prediction in resected NSCLC patients. Methods: This prospective cohort study recruited 116 patients with NSCLC following surgery and/or adjuvant therapy. Thirteen patients discontinued, leaving 103 patients for analysis. Tumor samples were obtained at surgery. Plasma samples were collected at baseline, after surgery, after adjuvant therapy and every 3 months thereafter and were analyzed by ultradeep (30000×) next-generation sequencing with molecular barcode and in-silico error correction. Results: Pretreatment ctDNA was detected in 69.8% of patients. ctDNA positivity after surgery and after completion of adjuvant chemotherapy (ACT) were significantly associated with worse recurrence-free survival (RFS) (HR: 4.0; 95% CI: 2.0-8.0; P&lt;.001 and HR:3.2; 95% CI: 1.3-8.2; P &lt;.05, respectively). In stage II-III patients who were positive for ctDNA after surgery, ACT-treated patients had a better RFS than those without ACT ( P&lt;.05), whereas ACT did not confer significant clinical benefits in patients with negative postsurgical ctDNA. During surveillance after definitive therapy, ctDNA positivity was associated with worse RFS (HR: 8.5, 95% CI: 3.7-20, P &lt;.001) and preceded radiological recurrence by a median of 88 days. Using joint modeling of serial ctDNA and time-to-recurrence, we accurately predicted patients’ 12-month and 15-month recurrence status, with areas under receiver-operating characteristics curves (AUROC) of 0.88 and 0.84, respectively. Conclusions: These results indicate that ultradeep ctDNA sequencing could sensitively detect MRD, thus identifying patients with high recurrence risk and guiding the adjuvant therapy decision in resected NSCLC. We also demonstrate that joint modeling of serial ctDNA levels and time to recurrent can provide an accurate dynamic risk prediction for NSCLC patients during surveillance. Clinical trial information: ChiCTR1900024656.

Multigene tests for breast cancer: the physician's perspective.

Breast cancer is the most common tumour in women and the first cause of death for cancer in the female population. Preserving the quality of life has therefore become an important objective in the management of the disease. The benefits of adjuvant chemotherapy in patients with HR+ HER2- early breast cancer should always be balanced against its potential short and long-term adverse effects, and identifying the appropriate patients for whom chemotherapy can offer the highest clinical benefit is critical. Besides clinical and pathological factors, today four multigene tests able to guide the choice of the adjuvant therapy early breast cancer are available in Italy: Oncotype DX®, EndoPredict®, MammaPrint® e Prosigna®. This review evaluates the main characteristics of these diagnostic tests, the studies on clinical utility, their economic impact and their inclusion in international and national guidelines. The Oncotype DX Breast Recurrence Score® test is the only multigene test validated, with level IA evidence, to guide the adjuvant therapy decisions: hormone therapy alone for most patients with RS results 0–25, and chemotherapy for patients with RS results 26–100. Clinical data demonstrate that the Oncotype DX test is able to significantly impact therapeutic decisions, reducing chemotherapy use up to 49% and supporting the use of chemotherapy (up to 12%) in potentially under-treated patients. Based on the level of clinical evidence and established clinical utility, several multigene tests have been included in the main international guidelines, with recommendations ranging from “strong” to “moderate”.

Prosigna test in breast cancer: real-life experience.

Genomic tests can guide the decision to administer adjuvant chemotherapy in women with hormone receptor (HR)-positive, Human Epidermal growth Factor 2 (HER2)-negative breast cancer (BC) at intermediate risk of recurrence. We assessed the decision-making and economic impact of the Prosigna test in a real-life setting. Retrospective cohort study of HR + , HER2- BC patients managed from 2016 to 2020, potential candidates for adjuvant chemotherapy, at intermediate risk of recurrence, in whom a Prosigna test was performed according to contemporary guidelines. The additional cost of chemotherapy over one year in terms of direct medical and non-medical costs was estimated in this study to be €9,737 (derived from a previous study, NCT02813317). The cost of the Prosigna test, as defined by the reimbursement system, was €1,849. Among the 809 patients included in this study, 2.3 Prosigna tests had to be performed to avoid adjuvant chemotherapy for one patient. The number of tests that had to be performed to avoid chemotherapy for one patient was higher for patients with grade 3 tumors and pN1mic axillary node involvement and lower for grade 1 tumors or in the absence of axillary node involvement (pN0), but did not vary according to the 10-year overall survival gain predicted by the Predict online test. The cost saving related to withholding of adjuvant chemotherapy for one patient on the basis of the Prosigna test results was €5,485. We present one of the largest cohorts of HR + , HER2- BC patients at intermediate risk of recurrence, in whom a Prosigna test was used to guide the adjuvant therapy decision in a real-life setting, resulting in a 44% decrease in the indication for chemotherapy.

Recurrence pattern and prognostic factors for survival in cervical cancer with lymph node metastasis.

The aim of this study is to evaluate the recurrence pattern and oncological outcomes in cervical cancer (CC) patients with lymph node metastasis. This study included 224 International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-IIIB CC patients with pathologically proven lymph node metastasis. Surgical intervention was grouped as hysterectomy performed/not performed. Adjuvant therapy decision was made by the tumor board. Radiotherapy was applied to all patients with lymph node metastasis. Only paraaortic lymph node metastasis was determined as an independent prognostic factor for recurrence. Presence of paraaortic lymph node metastasis increased the risk of recurrence more than two times (odds ratio: 2.129; 95% confidence interval: 1.011-4.485; p=0.047). An independent prognostic factor for death because of disease was age only. Risk of death was nearly doubled with younger age (odds ratio: 2.693; 95% confidence interval: 1.064-6.184; p=0.037). The most of recurrences were located at distant sites and multiple regions. Paraaortic lymph node metastasis was the only independent prognostic factor for recurrence, in spite of that age was an independent predictor for risk of death in patients with early stage or locally advanced CC and also with surgically proven metastatic lymph nodes. Furthermore, the presence of the paraaortic lymph node metastasis was significantly associated with distant recurrence. Therefore, more appropriate and individualized therapy strategy focusing on intenser systemic chemotherapy options in addition to radiotherapy should be taken into consideration according to paraaortic lymph node metastasis and age.

Prognostic value of intraductal carcinoma for adjuvant radiotherapy candidates after radical prostatectomy.

To investigate the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens and predictive value of IDC-P for biochemical recurrence and adjuvant therapy decision. We retrospectively evaluated patients who were performed RP between 2000 and 2014. Among, 67 patients who had stage pT3a tumour with negative surgical margin (Group 1, n=35) and who had stage pT2 tumour with positive surgical margin (Group 2, n=32) were included in the study. RP specimens were re-evaluated for the presence of IDC-P component and other prognostic factors. In both the groups, prognostic factors were compared according to the presence of IDC-P and biochemical recurrence status. In Group 1, IDC-P was detected in five cases and biochemical recurrence was detected in three cases. Patients with IDC-P showed significantly higher biochemical recurrence than those without IDC-P (P=.002). In univariate analysis, IDC-P was found to be significantly associated with worse progression-free survival (P<.001). In Group 2, IDC-P was detected in four cases and biochemical recurrence was detected in 10 cases. Also, tumour volume was significantly higher in patients with IDC-P than those without IDC-P (P=.02). IDC-P was also significantly associated with worse progression-free survival in Group 2 (P=.033). In both the groups, IDC-P was a prognostic factor for progression-free survival and/or biochemical recurrence. Especially in these patients, the presence of IDC-P might be helpful for postoperative adjuvant therapy management decision.

Abstract PS6-03: Prognostic value of clinical treatment score post-5 years (CTS5) and late relapse risk in hormone receptor-positive HER2-positive breast cancer in the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) and NSABP B-31 (NRG) trials

Abstract Background: Although risk of late relapse in hormone receptor-positive (HR+) breast cancer is well established, most existing data pertain to the HR+ HER2-negative (HER2-) subgroup. CTS5 is one of the models for predicting risk of late relapse in HR+ HER2- breast cancer. However, the value of this model in HR+ HER2+ disease is less known, particularly in the context of adjuvant trastuzumab. Here, we evaluated CTS5 in patients with early stage HR+ HER2+ breast cancer treated in the NCCTG N9831 (Alliance for Clinical Trials in Oncology) and NSABP B-31 (NRG) trials. Methods: Stage I-III HR+ (ER+ and/or PR+) HER2+ breast cancer patients who were free of recurrence after 5 years in N9831 and B-31 trials were included. The online CTS5 calculator was used to determine CTS5 score and risk group (low, intermediate, and high) based on age, tumor size, grade, and number of involved nodes. Kaplan-Meier (KM) estimates, Cox regression models, and C index were used for analysis. N9831 and B-31 trials were analyzed separately. Results: 1,204 patients in N9831 and 658 patients in B-31 met the entry criteria. Baseline characteristics were similar between both trials, including median age, tumor size, and follow up. Similar distribution within CTS5 risk group was observed in both trials; 68.2% and 70.1% patients were high risk, 24% and 21.9% as intermediate risk, as well as 7.8% and 8.1% as low risk classified in N9831 and B-31, respectively. Using univariate Cox regression analysis, CTS5 score as a continuous variable was associated with recurrence-free survival (RFS) in the entire study cohort, including patients who received chemotherapy alone or in combination with trastuzumab, (HR 1.37, 95%CI 1.03-1.81, p=0.03, C index 0.57 in N9831 and HR 1.36, 95%CI 1.06-1.76, p=0.02, C index 0.54 in B-31), but not in patients who received concurrent trastuzumab (HR 1.19, 95%CI 0.73-1.2, p=0.49, C index 0.54 in N9831 and HR 1.35, 95%CI 0.96-1.9, p=0.08, C index 0.54 in B-31). As categorical variable in the entire study cohort, CTS5 risk group was not significantly associated with RFS among patients with intermediate vs. low (HR 0.47, 95%CI 0.18-1.22, p=0.12 and HR 1.61, 95%CI 0.66-3.92, p=0.29) and high vs. low (HR 1.23, 95%CI 0.57-2.67, p=0.6 and HR 1.93, 95%CI 0.85-4.41, p=0.12) with the C index of 0.58 and 0.53 in N9831 and B-31 respectively. There was also no significant difference in RFS among 3 CTS5 risk groups with Kaplan-Meier estimates. Among patients who received concurrent trastuzumab, similar trends were observed with no statistical difference in RFS between high vs. low (HR 0.68, 95%CI 0.24-1.97, p=0.48 and HR 1.44, 95%CI 0.52-3.96, 0.49) with the C index of 0.55 and 0.51 in N9831 and B-31, respectively. Paradoxically, patients with intermediate risk had better RFS than low risk (HR 0.18, 95%CI 0.03-0.97, p=0.05) in N9831 but no significant difference in B-31 (HR 1.31, 95%CI 0.44-3.95, p=0.63). Conclusions: While CTS5 score as a continuous variable was associated with outcome in overall HR+ HER2+ population, this model was not prognostic in patients receiving adjuvant trastuzumab in both N9831 and B-31 trials. Furthermore, the correlation (C index) was modest and CTS5 risk group as a categorical variable could not stratify outcome in this group of patients. This study underlines the need to develop a new prognostic model to better delineate the risk of late relapse in HR+ HER2+ breast cancer patients receiving trastuzumab as this model can facilitate clinical decision for extended adjuvant endocrine therapy. Support: BCRF-19-161, U10CA180821, U10CA180868 and U10CA180822 (NRG), Genentech. https://acknowledgments.alliancefound.org Citation Format: Tanyami Pai, Angelica Gil, Yaohua Ma, Zhuo Li, Pooja Advani, Moreno Moreno-Aspitia, Gerardo Colon-Otero, Edith A. Perez, Yan Asmann, Katherine Pogue-Geile, E. A. Thompson, Saranya Chumsri. Prognostic value of clinical treatment score post-5 years (CTS5) and late relapse risk in hormone receptor-positive HER2-positive breast cancer in the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) and NSABP B-31 (NRG) trials [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 PS6-03.

Abstract PD4-06: How often does retrieval of a clipped lymph node change adjuvant therapy recommendations? A prospective consecutive patient cohort

Abstract Objectives and Rationale: For breast cancer patients receiving neoadjuvant chemotherapy (NAC) and undergoing pre-NAC axillary lymph node biopsy, NCCN guidelines recommend biopsy marker (clip) placement. This recommendation is based on reports that retrieval of the clipped node after NAC minimizes the false negative rate of sentinel lymph node biopsy (SLNB). Prior studies examining this practice in cN1 patients have reported that the clipped node is a non-SLN 20% of the time. There is limited data regarding if the clipped node needs to be retrieved among cN0 patients, and how often the post-NAC pathologic status of the clipped node has potential to change adjuvant therapy decisions. Here we aim to determine: 1) how often the clipped node is a non-SLN among both cN0 and cN1 patients, and 2) how often the retrieved, clipped node is a non-SLN and is the only positive node after NAC, potentially impacting adjuvant treatment recommendations. Methods: A consecutive cohort of 147 patients treated with NAC and surgery at our institution between January 2019-May 2020 was prospectively examined. Prior to NAC, all patients underwent routine axillary ultrasound (AxUS). For those with an abnormal appearing node, biopsy was performed of the most suspicious lymph node and a clip was placed. All cN0 patients underwent SLNB without localization of the clipped node. Patients who converted from cN1 to cN0 underwent radioactive seed localization of the clipped node and SLNB with dual tracers (radioactive tracer and blue dye). All lymph nodes were analyzed by IHC. Any residual disease, including ITCs, was considered pathologic node positive (ypN+). Patients with DCIS/unknown breast tumor histology (N = 3), those without AxUS (N = 9), those treated with neoadjuvant endocrine therapy (N = 9) and cN1 patients without a clip (N = 2) were excluded. Descriptive analyses were performed to examine the rate of ypN+ disease among cN0 and cN1 patients, and how often the clipped node was a non-SLN containing residual disease. In the cN0 population, if the clipped node was not obtained during SLNB it was considered a non-SLN. Results: Of 124 patients meeting study criteria, 61 were cN0 and 63 cN1. Among cN0 patients, 21 (34%) had suspicious lymph nodes on AxUS which were biopsied (negative) and clipped. All cN0 patients underwent successful SLNB, with a median of 2 SLNs removed (range 1-10). Of these, 5 (8%) were ypN+. Of the 21 patients with clipped nodes, 14 (67%) of the clipped nodes were non-SLN. If &amp;lt;3 SLNs were sampled, the clipped non-SLN rate was 82% (9/11). If ≥3 were sampled, the clipped non-SLN rate was 50% (5/10). Among patients with clipped nodes and ypN+ disease, there were no cases in which the clipped node was the only positive node. Among 63 cN1 patients with clipped nodes, 55 (87%) converted to cN0 and underwent SLNB. SLNB was successful in 52/55 (95%) and a median of 3 SLNs were removed (range 1-8). Overall, 28/55 (51%) were ypN+. Of the 52 with successful SLNB, 15 (29%) of the clipped nodes were non-SLN. If &amp;lt;3 SLNs were sampled, the clipped non-SLN rate was 46% (6/13). If ≥3 were sampled, the clipped non-SLN rate was 23% (9/39). In one of 52 (2%) patients, the clipped non-SLN was the only positive node. Conclusions: In this prospective study, among cN0 patients with negative pre-NAC lymph node biopsies, the clipped node was frequently a non-SLN and pathologic status of the clipped node alone did not impact management. Among cN1 patients suitable for SLNB after NAC, although the clipped node was a non-SLN 29% of the time, it was the only positive node in only one patient. The finding that the post-NAC pathologic status of the clipped lymph node alone potentially changed adjuvant treatment recommendations in only 2% (1/52) of patients warrants further investigation. Citation Format: Anna Weiss, Claire King, Samantha Grossmith, Leah Portnow, Sughra Raza, Faina Nakhlis, Laura Dominici, Elizabeth A. Mittendorf, Tari A. King. How often does retrieval of a clipped lymph node change adjuvant therapy recommendations? A prospective consecutive patient cohort [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 PD4-06.

Abstract PS5-34: Identification of proteomics-based biomarkers for ER+/HER2- breast cancer stratification: Implications on clinical outcome

Abstract Introduction: Improving stratification of breast cancer (BC) patients based on molecular signatures for treatment responses and clinical outcomes is a critical unmet need. Currently, endocrine therapy is first-line for hormone receptor positive (HR+) BC. Chemotherapy is added to patients with high-risk luminal BC. In practice, levels of Ki-67 are used to distinguish luminal tumors as low-risk luminal A (LA) and high-risk luminal B (LB) for adjuvant therapy decisions. Herein, proteomic tumor assessment from ER-positive HER2-negative (ER+/HER2-) BC patients was utilized to define molecular subtyping, estimate congruency between proteomic subtyping and traditionally used Ki67 marker, and define a new set of potential predictive and prognostic therapeutic biomarkers for ER+/HER2- BC patients. Method/Result: Clinical immunohistochemistry (IHC) subtyping of core biopsies was used to select a cohort of 86 BC patients with ER+/HER2- primary tumors from flash-frozen surgical samples. The positive/negative status of ER/PR/HER2 was defined using updated ASCO 2020 guidelines. Ki-67 status was determined using the 2011 St. Gallen’s International Expert Consensus recommendations. The cohort includes 28 LA (Ki67 &amp;lt; 14%) cases and 58 LB1 (Ki67 &amp;gt;= 14%) cases. Integrated consensus clustering algorithms with the most varying proteins in our cohort were applied to identify proteomic subtypes. Two distinct separations were observed from the analysis, resulting in one cluster enriched with LA (40 cases) and the other enriched with LB1 (46 cases) called by Fisher’s exact test. These clusters matched 100% with the clusters generated using 900+ proteins common to the 1500+ proteins used in the CPTAC-BC proteomics-based subtyping analysis (Mertins et al. Nature 2016). The differential analyses demonstrated that there is no significant difference between Ki67-defined subtypes and proteomics-defined subtypes (LA-enriched vs. LA cases, LB1-enriched vs. LB1 cases),indicating they are consistent in the molecular profile. Differential analysis was performed to compare LB1-enriched versus LA-enriched cases, resulting in 672 significantly differentially expressed proteins defined at false discovery rate (FDR) &amp;lt; 0.05 and |log2(fold change)|&amp;gt;1. 353 of the 672 proteins were correlated with mRNA at Pearson correlation &amp;gt; 0.39 as reported in the CPTAC-BC study or cBioPortal for Cancer Genome, and their coding genes were used for progression free interval (PFI) analysis based on TCGA RNA-seq data in the TCGA ER+/HER2- cases (662 cases, c.f. Huo et al. JAMA Oncology 2017). 90 of the 353 coding genes significantly associated with PFI were detected at p-value&amp;lt;0.05. Unsupervised hierarchical clustering method and principal component analysis (PCA) of the 90 genes were applied to our cohort to investigate the clustering performance and 94.2% of the cases were clustered correctly using support vector machine (SVM) method after PCA analysis. Biological process and molecular function GO term over-representation analyses of the 90 coding genes were performed separately. Some significant and biologically meaningful GO terms were identified at FDR&amp;lt;0.05. Conclusions: We identified a set of biomarkers that can be potentially employed as proteomic or gene signatures to stratify ER+/HER2- BC into low risk and high-risk groups. Disclaimers The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions, or policies of Uniformed Services University of the Health Sciences, The Henry M Jackson Foundation for the Advancement of Military Medicine Inc., the Department of Defense or the Departments of the Army, Navy or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. Citation Format: Guisong Wang, Punit Shah, Rick Searfoss, J. Leigh Fantacone Campbell, Jeffrey A. Hooke, Brenda Deyarmin, Rebecca N. Zingmark, Stella Somiari, Jianfang Liu, Leonid Kvecher, Lori A. Sturtz, Praveen-Kumar Raj-Kumar, Elder Granger, Linda Vahdat, Mary L. Cutler, Rangaprasad Sarangarajan, Hai Hu, Michael A. Kiebish, Albert J. Kovatich, Niven R. Narain, Craig D. Shriver. Identification of proteomics-based biomarkers for ER+/HER2- breast cancer stratification: Implications on clinical outcome [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 PS5-34.

Abstract PD4-02: Sentinel node biopsy should not be routine in older patients with ER positive breast cancer

Abstract Background:Based on randomized controlled trials demonstrating no survival benefit of axillary dissection in elderly breast cancer patients, the SSO/Choosing Wisely campaign recommended against the routine use of sentinel lymph node biopsy (SLNB) in clinically node negative patients aged ≥70 with estrogen receptor (ER) positive breast cancer in 2016. SLNB is still performed in &amp;gt;80% of such patients and we have previously shown that at our institution, SLNB positivity influences adjuvant therapy decisions in this population. In this study, we sought to validate the association of SLNB positivity and adjuvant treatment in a larger population-based cohort, and to evaluate the impact of this finding on oncologic outcomes. Methods:The Breast Cancer Outcome Unit (BCOU) prospectively collects demographic, pathologic, treatment and outcomes data on all patients referred to BC Cancer with breast cancer in British Columbia, Canada. Female patients aged ≥70 with newly diagnosed estrogen receptor-positive invasive breast cancer who underwent SLNB from 2010-2016 were included. Patients with HER2-positive disease or those treated with neoadjuvant therapy were excluded. Multivariable analysis was used to assess the effect of SLNB positivity on adjuvant treatment. Overall survival (OS) and breast cancer specific survival (BCSS) were assessed using Kaplan-Meier analysis and Cox regression was used to assess contribution of SLNB positivity and adjuvant treatment. A nomogram was created to model the effect of nodal positivity and adjuvant treatment on BCSS. Results:We identified 2580 patients who met study criteria with a median age of 75 and a median tumor size of 15 mm. SLNB was positive in 23%. Sixty-seven percent of patients had breast conserving surgery (BCS) and 62% of patients had RT (BCS 79%, mastectomy 25%). As systemic therapy 5% of patients had chemotherapy (CT) and 78% of patients had hormone therapy (HT). Use of adjuvant therapies was associated with SLNB positivity: Systemic therapy (HR = 2.4, 95% CI: 1.84-3.14, p &amp;lt;0.0001), RT (HR = 4.94, 95% CI: 3.91-6.25, p &amp;lt;0.0001) and nodal RT (HR = 61.4, 95% CI: 26.6-141.7, p &amp;lt;0.0001). The 5-year OS was 86% and BCSS was 96% with a median follow-up of 4.33 years (95% CI 4.21-4.47 years). There was improved BCSS with receipt of HT (HR 0.51 95% CI 0.301-0.875, p=0.0142) and worse BCSS with grade 3 vs grade 1 disease (HR 4.09, 95% CI 2.06-8.10, p&amp;lt;0.0001). Age, tumor size, status of SLNB and use of RT were not significant prognostic variables. Patients with a positive SLNB who did not receive any adjuvant therapy had lower BCSS (HR 3.22 95% CI 1.235-8.418, p=0.0168) than those with a negative SLNB. However, amongst those who received any combination of CT, HT and RT, there was no significant difference in BCSS regardless of nodal status. A nomogram was developed incorporating tumor size, grade, SLNB status and adjuvant treatment. Using the nomogram, patients aged 75-79 with T1, grade 1-2 tumors, with or without positive SLNB and treated with or without adjuvant therapy had 5-year BCSS ≥95%. The nomogram also indicated that 5-year BCSS was similar for patients with positive and negative SLNB for all combinations of tumor features when patients received HT. Conclusions:In this modern, population-based cohort of patients over 70 with ER-positive breast cancer, 5-year BCSS was excellent at 96%. Although the use of adjuvant treatment was associated with a positive SLNB, BCSS was not changed based on nodal status when patients received HT. Our results support the Choosing Wisely recommendations; SLNB can be safely omitted in elderly patients willing to take HT, and we advocate that SLNB can be omitted in low-risk patients aged ≥75 even in the absence of planned HT. Citation Format: Elaine McKevitt, Rona Cheifetz, Kimberly DeVries, Alison Laws, Rebecca Warburton, Lovedeep Gondara, Caroline Lohrisch, Alan Nichol. Sentinel node biopsy should not be routine in older patients with ER positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-02.

Pathological response post neoadjuvant therapy for locally advanced rectal cancer is an independent predictor of survival.

Neoadjuvant treatment (NaT) for locally advanced rectal cancer prior to surgery has led to improved outcomes. However, the relationship between pathological response to NaT and survival is not entirely clear. The aim of this study was to assess the degree of pathological response to NaT on survival outcomes. Clinical and pathological data were collected from a prospectively maintained pathology database between 2005 and 2017. The primary outcome was the overall survival based on pathological response categorized as complete, good partial, partial and minimal. Univariate and multivariate analyses were conducted to identify variables predictive of survival. Cox proportional hazard ratios were used for survival. A total of 596 patients had surgery following NaT for locally advanced rectal cancer. The median follow-up was 4.57years (interquartile range 2.21-8.15years). The overall survival for complete pathological response was 75.6% vs. 37.3% for minimal response (P<0.001). The overall survival at the end of the study in the good partial vs. partial response groups was 58.9% vs. 39% (P<0.001). On multivariate analysis, the degree of pathological response remains an independent variable for overall and disease-specific survival across all categories. In addition to other pathological variables, the degree of pathological response to NaT is an independent predictor for survival outcomes. Future verification of these findings elsewhere could support NaT response being used for adjuvant therapy decision making.

Characteristics and outcomes for fecal occult blood test (FOBT) screen detected (SD) versus non-screen detected (NSD) colorectal cancer (CRC).

42 Background: FOBT based screening for CRC has been shown in multiple studies to reduce CRC mortality. Beyond the well described earlier stage at diagnosis, other characteristics of SD cancers have not been well studied. Since 2006 Australians aged 50-74 have regularly been mailed an immunochemical FOBT via the National Bowel Cancer Screening Program (NBCSP), with participation rate stable around 40%. Methods: To explore patient (pt), tumour, treatment and outcome data for SD compared to NSD, we examined a multi-site CRC database where prospectively collected data includes method of detection. Categories include SD via the NBCSP, cases that were symptomatic or incidentally found on imaging (NSD), and cases detected by screening outside the NBCSP (OSD). High risk features for Australian Clinicopathological Staging System (ACPS) Stage B included emergency presentation, T4, lymphovascular invasion and &lt;12 lymph nodes examined. Results: Of 6969 registry pts diagnosed 06/2006–06/2020, 4107 (59%) were aged 50-74, including 473 (12%) SD, 3228 (79%) NSD and 406 (10%) OSD. SD versus NSD pts were younger (mean 62.4 v 64.2 years), had better ASA score (ASA 1-2: 79% v 66%, Odds Ratio [OR] 1.9, p&lt;0.001), earlier stage at diagnosis (ACPS A/B/C/D = 38%/21%/28%/5% v 17%/29%/26%/21%, p&lt;0.001), were more often left-sided (41% v 33%, OR 1.44, p&lt;0.001) but less frequently located in the rectum (28% v 36% OR 0.70, p=0.001). There was no difference by gender. SD tumors were more often well/moderately differentiated (76% v 66%, OR 1.65, p&lt;0.001) and less often mucinous (16% v 20%, OR 0.66, p=0.002). SD stage A tumours were more often T1 (66% v 43%, OR 0.36, p&lt;0.001). SD stage B tumours were more often T3 (92% v 85%, OR 0.43, p=0.033), and had fewer high risk features (60% v 49%, OR 0.64, p=0.036). SD stage C pts had a similar rate of N2 disease (25% v 31%, p=0.20), but more often received adjuvant chemotherapy (96% v 86%, OR 3.6, p=0.002). De novo stage D and relapsed SD pts more often underwent metastatic resection (46% v 25%, OR 2.6, p&lt;0.001). Relapse free survival (RFS) in stage A-C, progression free survival in stage D (PFS), and overall survival (OS) was superior for SD and is in Table. Conclusions: We show for the first time to our knowledge that SD CRCs have many distinct and favourable prognostic features that appear to be driving favourable stage based outcomes when compared to NSD patients. This prognostic data could inform adjuvant therapy decision making and surveillance strategies for SD CRC. [Table: see text]