Nomograms Integrating Body Composition Metrics Predict Total Pathologic Complete Remission after Neoadjuvant Systemic Therapy for Breast Cancer.

Background: Response to neoadjuvant chemotherapy (NAC) is a useful prognostic marker for relapse and overall survival but their prognostic role is distinct in different breast cancer subtypes. Pathologic complete response (pCR) is a current gold standard for evaluating response to NAC. Despite its clinical usefulness, discrimination into pCR and non-pCR is too simple because non-pCR includes broad range of actual responses from very good partial response to even progressive disease. American Joint Committee on Cancer (AJCC) 7th edition proposed response criteria for NAC based on precise clinical stage before NAC and pathologic staging after NAC. The purpose of this study is to evaluate the clinical usefulness of AJCC response criteria in each breast cancer subtypes. Patients and Methods: Patients with clinical stage II or III breast cancer treated with NAC at Seoul National University Hospital were enrolled and reviewed retrospectively. AJCC response criteria for NAC were adopted from the AJCC 7th edition: complete response (CR), absence of invasive carcinoma in both breast and lymph node; partial response (PR), decrease in either or both T or N stage; no response (NR), no change or increase in either or both T or N stage. The definition of each breast cancer subtypes were adopted from 2011 St Gallen Consensus Panel for current study. Results: From January 2009 to December 2010, 183 patients were enrolled in the study with median follow up period of 38.0 months. AJCC response was significantly associated with relapse free survival (RFS) (P<0.001), whereas pCR was not (P=0.120). In subgroup analysis, AJCC response was a significant prognostic factor for RFS in luminal B (P<0.001), HER-2 enriched (P=0.035) and triple negative breast cancer (P=0.037) groups, but not in luminal A group patients (P=0.101). On the contrary, pCR was not significantly associated with RFS in any groups. Conclusion : AJCC criteria is an easily reproducible tool for response evaluation for breast cancer patients in NAC setting compared with classically used pCR in all breast cancer subgroups except luminal A. Citation Format: Yaewon Yang, Seock-Ah Im, Tae-Yong Kim, Kyung-Hun Lee, Bhumsuk Keam, Sae-Won Han, Do-Youn Oh, Tae-You Kim, Wonshik Han, Hyeong-Gon Moon, In Ae Park, Dong-Young Noh. Different clinical usefulness of AJCC response criteria according to the subtypes in stage II/III breast cancer patients after neoadjuvant chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-15.

Neoadjuvant systemic therapy (NAST) has become an established treatment option for women with operable breast cancer. We aimed to better understand NAST treatment patterns, barriers and facilitators in Australia and New Zealand. We undertook a cross-sectional survey of the current clinical practice of Australian and New Zealand breast cancer specialists. Questions included referral patterns for NAST, patient selection, logistics, decision making and barriers. Of 207 respondents, 162 (78%) reported routinely offering NAST to selected patients with operable breast cancer (median 9% of patients offered NAST). Specialty, location, practice type, gender or years of experience did not predict for offering NAST. In all, 45 and 58% wanted to increase the number of patients who receive NAST in routine care and in clinical trials respectively. Facilitators included the multidisciplinary team meeting and access to NAST clinical trials. Specialist-reported patient barriers included: patient desire for immediate surgery (63% rated as important/very important); lack of awareness of NAST (50%); concern about progression (43%) and disinterest in downstaging (32%). Forty-three per cent of participants experienced system-related barriers to the use of NAST, including other clinicians' lack of interest (27%); lack of clinical trials (24%) and unacceptable wait for a medical oncology appointment (37%). This group of Australian and New Zealand clinicians are interested in NAST for operable breast cancer in routine care and clinical trials. Patient- and system-related barriers that prevent the optimal uptake of this treatment approach will need to be systematically addressed if NAST is to become a more common approach.

Recently, the American Joint Committee on Cancer (AJCC) 7th edition proposed new response criteria for neoadjuvant chemotherapy (NAC) in breast cancer. The purpose of this study was to evaluate the clinical usefulness of AJCC response criteria. A total of 398 consecutive stage II or III breast cancer patients who received NAC were enrolled in this study. AJCC response criteria were as follows: (1) complete response (CR)-absence of invasive carcinoma in the breast and node; (2) partial response (PR)-decrease in either or both T or N stage; (3) no response (NR)-no change or increase in either or both T or N stage. Complete response, PR, and NR by AJCC criteria were 9.8, 59.3, and 30.7 %, respectively. Among the 398 patients, 337 patients were available for both paired pre- and post- breast MRI and chest CT. AJCC response criteria were significantly associated with RECIST criteria (P < 0.001). AJCC response was significantly associated with relapse-free survival (RFS) and overall survival (OS). The 5-year RFS rates were 89.6 % in CR, 74.1 % in PR, and 62.6 % in NR (P = 0.002). The 5-year OS rates were 97.4 % in CR, 88.6 % in PR, and 78.3 % in NR (P = 0.012). When adjusting potential prognostic factors, AJCC response was independently associated with RFS and OS. AJCC response criteria for NAC in breast cancer have clinical usefulness in evaluating response of NAC, as well as predicting survival. AJCC response criteria can discriminate among patient subgroups with respect to survival.

ObjectivesThis study investigates the association between baseline CT body composition parameters and clinical outcomes in patients with resectable non-small cell lung cancer (NSCLC).MethodsPatients who underwent surgical resection for NSCLC between January 2006 and December 2017 were retrospectively enrolled in this multicenter study. Body composition metrics, including the area of skeletal muscle, intermuscular adipose tissue, subcutaneous adipose tissue, visceral adipose tissue, muscle radiodensity, and derivative parameters from five basic metrics mentioned before, were calculated based on preoperative non-contrast-enhanced chest CT images at L1 level. The Cox proportional hazards regression analysis was used to evaluate the association between body composition metrics and survival outcomes including overall survival (OS) and disease-free survival (DFS).ResultsA total of 2712 patients (mean age, 61.53 years; 1146 females) were evaluated. A total of 635 patients (23.41%) died. 465 patients (19.51%) experienced recurrence and/or distant metastasis. After multivariable adjustment, skeletal muscle index (SMI, HR = 0.86), intermuscular adipose index (IMAI, HR = 1.49), and subcutaneous adipose index (SAI, HR = 0.96) were associated with OS. Similar results were found after stratification by gender, TNM stage, and center. There was no significant association between all body composition metrics and DFS (all p > 0.05). The body composition metrics significantly enhance the model including clinicopathological factors, resulting in an improved AUC for predicting 1-year and 3-year OS, with AUC values of 0.707 and 0.733, respectively.ConclusionsSMI, IMAI, and SAI body composition metrics have been identified as independent prognostic factors and may indicate mortality risk for resectable NSCLC patients.Critical relevance statementOur findings emphasize the significance of muscle mass, quality, and fat energy storage in clinical decision-making for patients with non-small cell lung cancer (NSCLC). Nutritional and exercise interventions targeting muscle quality and energy storage could be considered for patients with NSCLC.Key PointsMultiparameter body composition analysis is associated with the clinical outcome in NSCLC patients.Assessing muscle mass, quality, and adipose tissue helps predict overall survival in NSCLC.The quantity and distribution of body composition can contribute to unraveling the adiposity paradox.Graphical

Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 36 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (&amp;lt; 10% positive cells in IHC) and PgR-negative (&amp;lt; 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2023 -Primary outcome analysis: Q1/2027 Current accrual: In June 2022, 150 patients were recruited in Germany and Italy. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy) Citation Format: Toralf Reimer, Thorsten Kuehn, Angrit Stachs, Anke Kleine-Tebbe, Nikola Bangemann, Andrea Stefek, Carolin Hammerle, Jörg Heil, Antje Nixdorf, Gabriele Bonatz, Agnieszka Nolte, Isabel T. Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Davide Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-07-01.

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.

Neoadjuvant systemic therapy (NAST) can be used to treat breast cancer. Pathologic complete response (pCR) is a surrogate marker for improved survival. This study examined response in the breast and axilla to NAST and identified features associated with pCR. Patients undergoing NAST and surgery between January 2012 and June 2016 by surgeons at Westmead Breast Cancer Institute were identified. Patients with inflammatory or metastatic disease were excluded. Data were analysed to identify factors predictive of pCR. Ninety-one patients were identified. Mean age was 49 years. Forty-one patients had axillary metastases identified prior to NAST. Eighty-three patients received chemotherapy alone, six endocrine therapy alone and two had both. Thirty-seven patients had mastectomy and 54 had breast-conserving surgery. The overall breast pCR rate was 29% higher in patients with triple-negative (50%) or HER2-positive (39%) disease and lower in luminal disease (11.6%, P = 0.001). Forty percent of node-positive patients became node negative. The only variable associated with pCR was tumour biology. Patients with HER2-positive breast cancer were more likely to have axillary pCR than those with luminal cancer (odds ratio: 28, P = 0.00005). pCR in either the breast or axilla was most likely to be achieved in patients with HER2-positive or triple-negative breast cancers. In patients with luminal cancers, the goal of NAST is best considered to facilitate surgical options rather than obtaining a pCR.

BackgroundAxillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT combined with pathological axillary treatment response has been proposed to guide de-escalation of axillary treatment for clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy. The aim of this study was to assess whether axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and breast cancer molecular subtype are predictors of axillary pCR.MethodsThis study included clinically node-positive patients treated with neoadjuvant systemic therapy in the prospective Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy (‘RISAS’) trial (NCT02800317) with baseline [18F]fluorodeoxyglucose PET/CT imaging available. The predictive value of axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and breast cancer molecular subtype to estimate axillary pCR was evaluated using logistic regression analysis. Discriminative ability is expressed using ORs with 95% confidence intervals.ResultsOverall, 185 patients were included, with an axillary pCR rate of 29.7%. The axillary pCR rate for patients with limited versus advanced baseline axillary disease according to [18F]fluorodeoxyglucose PET/CT was 31.9% versus 26.1% respectively. Axillary disease extent was not a significant predictor of axillary pCR (OR 0.75 (95% c.i. 0.38 to 1.46) (P = 0.404)). There were significant differences in axillary pCR rates between breast cancer molecular subtypes. The lowest probability (7%) was found for hormone receptor+/human epidermal growth factor receptor 2− tumours. Using this category as a reference group, significantly increased ORs of 14.82 for hormone receptor+/human epidermal growth factor receptor 2+ tumours, 40 for hormone receptor−/human epidermal growth factor receptor 2+ tumours, and 6.91 for triple-negative tumours were found (P < 0.001).ConclusionMolecular subtype is a significant predictor of axillary pCR after neoadjuvant systemic therapy, whereas axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT is not.

BackgroundThis study aimed to assess the influence of disease- and patient-related factors on surgeons’ decisions to refer patients with early-stage breast cancer (EBC) for neoadjuvant systemic therapy (NST).MethodsAn online survey of United States surgeons evaluated the influence of selected disease- and patient-related factors on surgeons’ decisions, rated their influence (individually and in combination), and provided a relative ranking of jointly considered factors using best–worst scaling.ResultsThe participants in this study were 100 licensed surgeons. The surgeons referred approximately 25 % of EBC patients for NST to improve surgical management. Approximately 75 % of the surgeons agreed that NST is important for EBC, if only to improve surgical management. More than half were “very likely” to refer EBC patients for NST based on anatomicopathologic factors. Less than 50 % were “very likely” to do so when considering tumor phenotype factors. Tumor size and lymph node status were ranked highest in hypothetical patient scenarios. Regarding combinations of factors, the importance of any single factor varied according to the combinations presented. Less than half of the respondents were “very familiar,” and half were “somewhat familiar” with NST guidelines for breast cancer. More than half of the respondents were unaware that findings have shown achievement of pathologic complete response (pCR) after NST to be associated with improved survival.ConclusionsSurgeons’ decision to refer for NST is strongly driven by surgical management goals. Anatomicopathologic factors are more influential than tumor phenotype. However, no single disease or patient factor consistently drives the decision to refer for NST. Surgeons’ awareness of the association between pCR achievement and longer survival could be improved.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-016-5296-y) contains supplementary material, which is available to authorized users.

Cells to Surgery Quiz: May 2019

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Poor body composition metrics (BCM) are associated with inferior cancer outcomes; however, in early breast cancer (EBC), there is a paucity of evidence regarding the impact of BCM on toxicities. This study investigates associations between BCM and treatment-related toxicity in patients with EBC receiving anthracyclines and taxane–based chemotherapy.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Pretreatment computerized tomographic (CT) images were evaluated for skeletal muscle area (SMA), skeletal muscle density (SMD), and fat tissue at the third lumbar vertebrae. Skeletal muscle index (SMI = SMA/height&lt;sup&gt;2&lt;/sup&gt;) and skeletal muscle gauge (SMG = SMI × SMD) were also calculated. Relative risks (RR) are reported for associations between body composition measures and toxicity outcomes, after adjustment for age and body surface area (BSA).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; BCM were calculated for 151 patients with EBC (median age, 49 years; range, 23–75 years). Fifty patients (33%) developed grade 3/4 toxicity, which was significantly higher in those with low SMI (RR, 1.29; &lt;i&gt;P&lt;/i&gt; = 0.002), low SMG (RR, 1.09; &lt;i&gt;P&lt;/i&gt; = 0.01), and low lean body mass (RR, 1.48; &lt;i&gt;P&lt;/i&gt; = 0.002). Receiver operating characteristic analysis showed the SMG measure to be the best predictor of grade 3/4 toxicity. Dividing SMG into tertiles showed toxicity rates of 46% and 22% for lowest versus highest tertile, respectively (&lt;i&gt;P&lt;/i&gt; = 0.005). After adjusting for age and BSA, low SMG (&lt;1,475 units) was significantly associated with hematologic (RR, 2.12; &lt;i&gt;P&lt;/i&gt; = 0.02), gastrointestinal grade 3/4 toxicities (RR, 6.49; &lt;i&gt;P&lt;/i&gt; = 0.02), and hospitalizations (RR, 1.91; &lt;i&gt;P&lt;/i&gt; = 0.05).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Poor BCMs are significantly associated with increased treatment-related toxicities. Further studies are needed to investigate how these metrics can be used to more precisely dose chemotherapy to reduce treatment-related toxicity while maintaining efficacy. &lt;i&gt;Clin Cancer Res; 23(14); 3537–43. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

BackgroundMarking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node‐positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment‐positive marked lymph nodes (MLNs) together with SLNs.MethodsThis was a multicentre retrospective analysis of patients with clinically node‐positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately.ResultsAt least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent).ConclusionExcision of the pretreatment‐positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node‐positive disease resulted in a higher identification rate and improved detection of residual axillary disease.

BACKGROUND: The current American Joint Committee on Cancer (AJCC) breast cancer staging system provides important prognostic information, however its use is limited by the lack of data incorporating prognostic and predictive biological markers. In this study we sought to determine the relationship between stage, breast cancer subtype, grade and outcome in a large population-based cohort, and to develop a risk score point-based system incorporating biological factors to the current AJCC staging system. METHODS: Patients diagnosed with primary breast cancer stage I-IV, between 2005-2008 were identified in the California Cancer Registry. For patients with stage I-III disease, pathological stage was recorded. For those with stage IV, clinical stage was used. 5 year-breast cancer specific survival (BCSS) and overall survival (OS) rates were determined for each potential TNM combination according to breast cancer subtype. Cox proportional hazard models were used to identify independent predictors of outcome. A risk score point-based system (range 0-3 points) was created to complement the current anatomic AJCC staging system. One point was assigned for each one of the following tumor characteristics: hormone receptor (HR)-negative status, HER2-negative status and grade 3. Survival probabilities between groups were compared using log-rank test. Multivariable analysis models according to stage and risk score were performed for BCSS and OS. RESULTS: A total of 43,938 patients were included. The 5-year BCSS and OS for each TNM combination differed according to breast cancer subtype. The best outcomes were seen among HR-positive patients followed closely by those with HER2-positive and HR-positive tumors with the worst outcomes observed among patients with triple negative tumors. In a multivariable model, after adjusting for stage, treatment variables and other important confounders, ER negative status (OR 2.14; 95%CI 1.98-2.30), HER2-negative status (OR= 1.24; 95%CI1.14-1.34) and grade 3 (OR=2.03; 95% CI 1.88-2.20) were independent predictors of BCSS. Our risk score system separated patients into 4 risk groups within each stage category (all P&amp;lt;0.05). Similar results were seen for OS. The results in the table show that combining stage and risk score provides improved prognostic information. Hazard ratios for BCSS according to stage and risk score.Stage/Risk ScoreHazard Ratio95%CII-0Reference I-10.630.42-0.97I-22.811.87-4.23I-34.902.79-8.61IIA-03.652.26-5.91IIA-12.241.50-3.33IIA-25.873.94-8.73IIA-39.356.24-13.99IIB-04.763.13-7.24IIB-15.043.37-7.53IIB-29.465.63-15.92IIB-314.599.78-21.79IIIA-09.136.12-13.62IIIA-17.384.92-11.06IIIA-212.017.14-20.19IIIA-332.5421.59-49.04IIIB-018.9712.62-28.52IIIB-119.0512.68-28.61IIIB-228.3418.91-42.47IIIB-335.6121.33-59.43IIIC-011.525.84-22.74IIIC-115.766.07-40.94IIIC-226.7716.74-42.83IIIC-356.6336.60-87.60IV-049.9330.64-81.36IV-167.4545.36-100.23IV-2107.6272.36-60.07IV-3164.04107.18-251.04 CONCLUSIONS: Incorporating biological factors to the current AJCC staging system provides more accurate prognostic information and reflects current treatment practice. The proposed risk score improves the AJCC breast cancer staging system and should be incorporated in the upcoming revision. Citation Format: Chavez-MacGregor M, Mittendorf EA, Clarke CA, Lichensztajn DY, Hunt KK, Giordano SH. Improving the AJCC breast cancer staging system by incorporating tumor biomarkers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-02.

The objective of this systematic review is to investigate the role of imaging in response monitoring during neoadjuvant systemic therapy (NST) for breast cancer and assess whether treatment modifications based on imaging response are implemented in clinical practice. A systematic review was conducted, analyzing five clinical practice guidelines and 147 clinical trial publications involving NST for breast cancer. The snowballing technique was employed, using a "start set" of clinical guidelines to trace relevant trials. Additionally, a PubMed search was conducted to identify trials published between 2023-2024. The review analyzed the use of imaging modalities, timing, and response criteria, and whether escalation, de-escalation, or change of treatment occurred based on imaging response. Imaging was utilized in 81% (119/147) of the trials, with ultrasound, MRI, and mammography being the most frequently employed modalities. Mid-treatment imaging was applied in 56% (83/147) of the trials. However, only 15% (22/147) of the trials implemented treatment modifications based on imaging response, highlighting the limited application of imaging response-guided therapy. No standardized imaging protocols or consistent response-guided treatment strategies were identified across the trials or clinical practice guidelines, with considerable variability in imaging methods, timing, and response criteria. This systematic review underscores the critical need for standardized imaging protocols, response assessment criteria and image-guided treatment decisions. It is therefore evident that imaging for response monitoring during treatment should preferably be performed within clinical trials.

Purpose To investigate the performance of tumor subtype and various magnetic resonance (MR) imaging parameters in the assessment of tumor response to neoadjuvant systemic therapy (NST) in patients with breast cancer and to outline a model of pathologic response, considering pathologic complete response (pCR) as the complete absence of any residual invasive cancer or ductal carcinoma in situ (DCIS). Materials and Methods This was an institutional review board-approved retrospective study, with waiver of the need to obtain informed consent. From November 2009 to December 2014, 111 patients with histopathologically confirmed invasive breast cancer who were undergoing NST were included (mean age, 54 years; range, 27-84 years). Breast MR imaging was performed before and after treatment. Presence of late enhancement was assessed. Apparent diffusion coefficients (ADCs) were obtained by using two different methods. ADC ratio (mean posttreatment ADC/mean pretreatment ADC) was calculated. pCR was defined as absence of any residual invasive cancer or DCIS. Multivariate regression analysis and receiver operating characteristic analysis were performed. Results According to their immunohistochemical (IHC) profile, tumors were classified as human epidermal growth factor receptor 2 (HER2) positive (n = 51), estrogen receptor (ER) positive/HER2 negative (n = 40), and triple negative (n = 20). pCR was achieved in 19% (21 of 111) of cases; 86% of them were triple-negative or HER2-positive subtypes. Absence of late enhancement at posttreatment MR imaging was significantly associated with pCR (area under the curve [AUC], 0.85). Mean ADC ratio significantly increased when pCR was achieved (P < .001). A κ value of 0.479 was found for late enhancement (P < .001), and the intraclass correlation coefficient for ADCs was 0.788 (P < .001). Good correlation of ADCs obtained with the single-value method and those obtained with the mean-value methods was observed. The model combining the IHC subtype, ADC ratio, and late enhancement had the highest association with pathologic response, achieving an AUC of 0.92 (95% confidence interval: 0.86, 0.97). Conclusion Triple-negative or HER2-positive tumors showing absence of late enhancement and high ADC ratio after NST are associated with pCR. © RSNA, 2016 Online supplemental material is available for this article.