Pathological Prognostic Staging Research Articles

Population Attributable Risk of Advanced-Stage Breast Cancer by Race and Ethnicity

Advanced-stage breast cancer rates vary by race and ethnicity, with Black women having a 2-fold higher rate than White women among regular screeners. Clinical risk factors that explain a large proportion of advanced breast cancers by race and ethnicity are unknown. To evaluate the population attributable risk proportions (PARPs) for advanced-stage breast cancer (prognostic pathologic stage IIA or higher) associated with clinical risk factors among routinely screened premenopausal and postmenopausal women by race and ethnicity. This cohort study used data collected prospectively from Breast Cancer Surveillance Consortium community-based breast imaging facilities from January 2005 to June 2018. Participants were women aged 40 to 74 years undergoing 3 331 740 annual (prior screening within 11-18 months) or biennial (prior screening within 19-30 months) screening mammograms associated with 1815 advanced breast cancers diagnosed within 2 years of screening examinations. Data analysis was performed from September 2022 to August 2023. Heterogeneously or extremely dense breasts, first-degree family history of breast cancer, overweight/obesity (body mass index >25.0), history of benign breast biopsy, and screening interval (biennial vs annual) stratified by menopausal status and race and ethnicity (Asian or Pacific Islander, Black, Hispanic/Latinx, White, other/multiracial). PARPs for advanced breast cancer. Among 904 615 women, median (IQR) age was 57 (50-64) years. Of the 3 331 740 annual or biennial screening mammograms, 10.8% were for Asian or Pacific Islander women; 9.5% were for Black women; 5.3% were for Hispanic/Latinx women; 72.0% were for White women; and 2.0% were for women of other races and ethnicities, including those who were Alaska Native, American Indian, 2 or more reported races, or other. Body mass index PARPs were larger for postmenopausal vs premenopausal women (30% vs 22%) and highest for postmenopausal Black (38.6%; 95% CI, 32.0%-44.8%) and Hispanic/Latinx women (31.8%; 95% CI, 25.3%-38.0%) and premenopausal Black women (30.3%; 95% CI, 17.7%-42.0%), with overall prevalence of having overweight/obesity highest in premenopausal Black (84.4%) and postmenopausal Black (85.1%) and Hispanic/Latinx women (72.4%). Breast density PARPs were larger for premenopausal vs postmenopausal women (37% vs 24%, respectively) and highest among premenopausal Asian or Pacific Islander (46.6%; 95% CI, 37.9%-54.4%) and White women (39.8%; 95% CI, 31.7%-47.3%) whose prevalence of dense breasts was high (62%-79%). For premenopausal and postmenopausal women, PARPs were small for family history of breast cancer (5%-8%), history of breast biopsy (7%-12%), and screening interval (2.1%-2.3%). In this cohort study among routinely screened women, the proportion of advanced breast cancers attributed to biennial vs annual screening was small. To reduce the number of advanced breast cancer diagnoses, primary prevention should focus on interventions that shift patients with overweight and obesity to normal weight.

K-Ras4A Plays a More Significant Role than K-Ras4B in Ductal Carcinoma of Breast.

K-Ras mutations rarely occur in breast cancer. However, studies have supported that K-Ras upregulation is involved in breast cancer pathogenesis. Two main K-Ras transcript variants; K-Ras4A and K-Ras4B, originate from the alternative splicing of exon 4. In this study, we aimed to evaluate variations in the expression of K-Ras4A and K-Ras4B and their role in breast ductal carcinoma. Total RNA was extracted from breast tumors, and the NATs obtained via mastectomy. Patients were selected from new cases of breast cancer with no prior history of chemotherapy. Relative mRNA expression was calculated based on a pairwise comparison between the tumors and the NATs following normalization to the internal control gene. Predictive values of the transcript variants were examined by ROC curve analysis. A statistically significant increase was found in the K-Ras4A and K-Ras4B expression with the mean fold changes of 7.58 (p = 0.01) and 2.47 (p = 0.001), respectively. The K-Ras4A/K-Ras4B ratio was lower in the tumors than that of the normal tissues. ROC curve analysis revealed the potential of K-Ras4A (AUC: 0.769) and K-Ras4B (AUC: 0.688) in breast cancer prediction. There was also a significant association between K-Ras4B expression and HER2 statues (p = 0.04). Furthermore, a significant link was detected between K-Ras4A expression and pathological prognostic stages (p = 0.04). Our findings revealed that expression levels of K-Ras4A and K-Ras4B is higher in the tumor compared to the normal breast tissues. Increase in K-Ras4A expression was more significant than that of K-Ras4B.

Prognostic impact of 18F-FDG PET/CT in pathologic stage II invasive ductal carcinoma of the breast: re-illuminating the value of PET/CT in intermediate-risk breast cancer

BackgroundThe aim of this study is to investigate the impact of 18F-FDG PET/CT on prognosis of stage II invasive ductal carcinoma (IDC) of the breast primarily treated with surgery.MethodsThe clinical records of 297 consecutive IDC with preoperative PET/CT and pathologically staged II in surgery from 2013 to 2017 were retrospectively reviewed. The maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), tumor-to-liver ratio (TLR), and metabolic tumor volume (MTV) were measured. Association of clinicopathologic factors (age, T stage, N stage, AJCC pathologic stage of IIA or IIB, pathologic prognostic stage, grade, hormonal receptor status, HER2 status, Ki-67, and adjuvant therapy) and PET parameters with DFS was assessed using the Cox proportional hazards model.ResultsThere were 35 recurrences and 10 deaths at a median follow-up of 49 months (range 0.8 ~ 87.3). All PET parameters were significantly associated with DFS in univariate analysis but in multivariate analysis, SUVpeak was the only factor significantly associated with DFS (hazard ratio 2.58, 95% confidence interval 1.29–5.15, P = 0.007). In cohorts with higher values of SUVpeak or TLR, patients who received adjuvant chemotherapy had significantly superior DFS.ConclusionMetabolic parameters derived from preoperative PET/CT was significantly associated with recurrence in stage II IDC primarily treated with surgery. PET/CT can be a powerful prognostic tool in conjunction with novel staging systems and current biomarkers for patients undergoing contemporary therapy. Our results urge to reconsider the currently underestimated value of PET/CT confined to diagnostic aspect and to newly recognize its prognostic impact in these intermediate-risk breast cancer.

Clinicopathological and prognostic characteristic features of triple negative and nontriple negative breast cancer at a tertiary care hospital.

Carcinoma breast is a complex disease having diverse clinical, histopathological, and immunohistochemical features. Basing on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2) status, these tumors are divided into triple-negative breast cancers (TNBC) where tumor cells are negative for all three receptors and nontriple negative breast cancer (non-TNBC) where tumor cells are positive for one or two or all. The clinicopathological and characteristic prognostic features are highlighted here. The aim of this study is to evaluate the clinicopathological and prognostic features of TNBC and non-TNBC cases diagnosed in our hospital setting. Single institution, retrospective study conducted over 7 and half years. Histopathologically confirmed breast cancer cases with ER, PR, and HER2 receptor assessment were categorized into TNBC and non-TNBC. Detailed study on clinicopathological and prognostic features including pathological prognostic stage as per 8th AJCC was done in cases who underwent modified radical mastectomy. Data were analyzed in percentage and presented in tables and charts. The present study included 794 cases consisting of 253, 31.9% TNBC and 541, 68.1% non-TNBC cases. The mean age of TNBC and non-TNBC cases was 50.4 years and 51.7 years, respectively. Coagulative necrosis, lymphovascular invasion, lymph nodal metastasis, higher histopathological tumor grade, and NPI were observed in higher percentage of TNBC cases, i.e., 19 (10.9%), 21 (11.6%), 105 (57.7%), 127 (69.8%), and 149 (81.9%) cases, respectively, than non-TNBC seen in 18 (6.6%), 24 (8.8%), 135 (49.6%), 165 (60.7%), and 194 (71.3%) cases, respectively. Further, 25 (13.7%) TNBC and 1 (0.4%) non-TNBC case were upstaged, whereas 130 (47.8%) non-TNBC and 2 (1.1%) TNBC cases were downstaged by the pathological prognostic stage. TNBC is more aggressive having a poor prognosis than non-TNBC.

Stage-Specific Survival in Breast Cancer in Chinese and White Women: Comparative Data Analysis.

Stage-specific survival, according to the eighth edition of the American Joint Committee on Cancer (AJCC) pathological prognostic staging (PPS) on breast cancer (BC), between Chinese and White American women remains unclear. This study aimed to assess stage-specific survival in BC between Chinese and White American women according to the eighth AJCC PPS. We included Chinese and White American women with BC diagnosed between 2010 and 2018 from the Surveillance, Epidemiology, and End Results database. A chi-square test, the Kaplan-Meier method, a receiver operating characteristic (ROC) curve, and multivariate Cox proportional hazards models were used for data analysis. We included 376,818 individuals in this study: 369,522 White American and 7296 Chinese. Of them, 149,452 (39.7%) migrated from the seventh AJCC anatomic staging (AS) to the eighth AJCC PPS, 22,516 (6.0%) were upstaged, and 126,936 (33.7%) were downstaged. With a median follow-up duration of 44 months, the 5-year overall survival and cancer-specific survival (CSS) for the entire group were 87.4% and 95.9%, respectively. The seventh AJCC AS (P<.001) and the eighth AJCC PPS (P<.001) could significantly predict the survival outcomes of BC, and multivariate analysis revealed that both staging systems were significant prognostic indicators of CSS. The ROC curve revealed that the PPS had a better discriminating ability than the AS (area under the curve [AUC] 0.769 vs 0.753, P<.001). Similar trends were observed after stratification by the 2 ethnic groups. The eighth AJCC PPS had better discriminating ability than the seventh AJCC AS among both White American (AUC 0.769 vs 0.753, P<.001) and Chinese patients (AUC 0.790 vs 0.776, P<.001). In the seventh AJCC AS, Chinese women had better CSS in stage IA (P=.02), stage IIA (P=.005), and stage IIIB (P=.04) disease than White American women, but no significant CSS was observed in stage IB, IIB, IIIA, and IIIC disease between the 2 ethnic groups. Regarding the eighth AJCC PPS, Chinese women had better CSS in stage IA (P=.002) and IIIA (P=.046) disease than White American women, and CSS was similar in Chinese and White American women in other substages. The eighth AJCC PPS has a similar discriminative ability between White American and Chinese individuals with BC compared with the seventh AJCC AS. Therefore, the eighth AJCC PPS is also applicable to Chinese individuals with BC.

The Value of the 8th Edition of American Joint Committee on Cancer Pathological Prognostic Staging on the Selection of Postmastectomy Radiotherapy for T1-2N1 Breast Cancer.

Patients diagnosed with pT1-2N1M0 breast cancer between 2008 and 2018 in West China Hospital, Sichuan University were included. Locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS) were defined as endpoints. The propensity score matching (PSM), receiver operating characteristic (ROC) curve, the Kaplan-Meier analysis, and the Cox multivariable model were used for data analysis. We identified 1,615 patients with T1-2N1M0 breast cancer, and 44.9% (n = 744) of them were treated with PMRT. With a median follow-up of 76 months, 46 (2.8%) recurrences, 96 (5.9%) deaths, and 80 (5.0%) breast cancer-related deaths occurred. The 5-year LRFS, DMFS, DFS, BCSS, and OS were 98.6%, 95.3%, 93.7%, 96.5%, and 96.0%, respectively. PMRT could not improve 5-year LRFS, DMFS, DFS, BCSS, and OS compared with non-PMRT neither before nor after PSM in the era of contemporary systemic treatment. ROC curve showed that the 8th pathological prognostic staging had better discriminative ability compared with the 7th anatomical staging [the area under the curve (AUC) 0.653 vs. 0.546, P < 0.001]. In the anatomical staging system, PMRT had comparable 5-year BCSS in comparison with non-PMRT both in stages IIA (97.4% vs. 96.8%, P = 0.799) and IIB (95.3% vs. 97.0%, P = 0.071). When stratified according to the pathological staging, PMRT was associated with better 5-year BCSS in stage IIB (97.1% vs. 90.7%, P = 0.039), while not in stages IA, IB, IIA, and IIIA. Multivariate analysis demonstrated that PMRT was a significantly protective factor for BCSS in stage IIB (HR 0.331, 95% CI: 0.100-0.967, P = 0.044). The new staging could better select high-risk patients with T1-2N1 breast cancer for radiotherapy compared with the 7th staging, and PMRT might be exempted except the 8th staging of IIB in the era of contemporary systemic therapy in this disease.

Combining Step-and-Shoot Intensity Modulated Radiation Therapy Concomitant Boost to Tumor Bed and 3D Breast Field-in-Field Plans for Hypofractionated Breast Radiotherapy

<h3>Purpose/Objective(s)</h3> To investigate the efficacy and safety of step-and-shoot intensity modulated radiation therapy (IMRT) concomitant boost (CB) to tumor bed (TB) combined with 3D breast field-in-field (FIF) plans for hypofractionated breast radiotherapy. <h3>Materials/Methods</h3> We initiated prospective cohort study since January, 2020. The patients with early-stage breast cancer or breast ductal carcinoma in situ who received breast-conserving surgery underwent sixteen-fraction treatment. All received prescribed dose of 40 Gy 3D FIF plans to breast, CB with 8 Gy to TB by IMRT. We applied the identical contours and PTV coverage to compare the original plans with the re-plans using conventional fractions of breast FIF followed by en face electron beams to TB on the same patients. Plan quality including maximum dose, RTOG conformal index (CI) and homogeneity index (HI) of PTV_TB, mean dose and volumes irradiated to doses of 5 Gy (V₅) of heart and V₂₀ of ipsilateral lung, in addition to acute toxicity and any recurrence were evaluated. Lyman normal tissue complication probability (NTCP) model for moderate to severe breast fibrosis established by Cambridge and EORTC trials was also calculated. Paired sample t-test and Wilcoxon signed-rank test were used. <h3>Results</h3> Thirty patients with sixty treatment plans were reviewed. The majority (19/30) were pathological prognostic stage I breast cancer and half of the patients were left-sided diseases. No patient experienced more than grade 2 acute toxicity. No recurrence was observed during the follow-up. Mean HI (D₂-D₉₈/D_p × 100; where D₂ = minimum dose to the 2% of the target volume, D₉₈ = minimum dose to the 98% of the target volume, and D_p = prescribed dose) of PTV_TB is 9.4 vs. 18.5 (<i>P</i> < .05). Maximum dose divided by reference dose was also lower in the CB group by 2.9% (<i>P</i> < .05). Mean CI is 1.45 in the CB group compared to 1.63 in the conventional fraction plans (<i>P</i> = .07). In terms of EQD2, mean dose and V₅ of heart for left-sided breast cancer are similar (<i>P</i> = .12 and 0.10). Besides, mean dose and V₂₀ of ipsilateral lung are comparable (<i>P</i> = .26 and 0.43). NTCP for breast fibrosis were all lower in the CB group (Mean: 20.02% vs. 22.13%; <i>P</i> < .05). <h3>Conclusion</h3> Hypofractionated breast radiotherapy combing 3D FIF plans and IMRT CB to TB decreased breast moderate to severe fibrosis by Lyman NTCP model and improved homogenous dose distributions without excessive dose to normal tissue, when compared to conventional fractions using FIF and electron beams. It may reduce the toxicity, and is also labor-saving for patients, radiation oncologists and staff.

The Clinicopathological Profile of Breast Cancer in Young Women from a Tertiary Care Center

Abstract Background Increasing number of young breast cancer patients are seen in India and many of these young breast cancer patients are considered to have more aggressive disease biology. Aim The aim of this article was to study the clinicopathological profile of breast cancer patients in the young and older patients to understand the difference between these two groups. Methods This was a retrospective study conducted on 421 breast cancer patients. Results Total of 421 breast cancer patients were studied, out of which 158 patients were less than or equal to 40 years age group and 263 patients were in more than or equal to 50 years age group. Commonest T stage on presentation was T2, which was seen 56.32% of young breast cancer patients and in 64.64% of older patients. Higher nodal spread was seen in younger patients when compared with older patients (p-value = 0.00001). Older group patients had significant decline from anatomical to pathological prognostic stage group compared with younger group (29 vs. 13.29%; p-value = 0.00001). Grade 3 tumors were seen in 58.23% of younger patients and 22.05% of older patients (p-value = 0.00001). Triple-negative breast cancer was seen more commonly in younger group compared with older group (p-value = 0.0088). Conclusions Significant number of breast cancer patients present in younger age group in India. Younger breast cancer patients tend to have higher grade tumors and triple-negative breast cancer is common in younger age groups. Pathological prognostic stage grouping appears clinically more relevant than anatomical stage groups.

The Predictive Effect of the 8th AJCC Pathological Prognostic Staging on the Benefit of Postmastectomy Radiotherapy in N2/N3 Breast Cancer.

BackgroundThe role of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging (PPS) on treatment-decision making of breast cancer (BC) remains unclear. This study aimed to investigate the predictive effect of the 8th AJCC PPS on the benefit of postmastectomy radiotherapy (PMRT) in N2/N3 BC.MethodsWe included women with stage N2/3 BC diagnosed between 2010 and 2018 from the Surveillance, Epidemiology, and End Results database. The effect of PMRT on breast cancer-specific survival (BCSS) was evaluated using the multivariate Cox proportional-hazards models.ResultsA total of 13,445 patients were identified, including 10,547 (78.4%) patients treated with PMRT. All patients had reassigned stages based on the 8th AJCC PPS. There were 7102 patients (52.8%) that had stage changed, including 1160 patients (8.6%) were upstaged and 5942 patients (44.2%) were downstaged from the 7th AJCC anatomical staging (AS) to the 8th AJCC PPS. Regarding the 7th AJCC AS, 7603 (56.5%), 948 (7.1%), and 4895 (36.4%) were stage IIIA, IIIB, and IIIC diseases, respectively. Using the 8th AJCC PPS, 3525 (26.2%), 460 (3.4%), 1335 (9.9%), 3457 (25.7%), 2169 (19.1%), and 2100 (15.6%) patients were restaged as IB, IIA, IIB, IIIA, IIIB, and IIIC diseases, respectively. The PPS displayed increased prognostic accuracy and improved model fit with respect to BCSS compared to the 7th AS (C-index, 0.731 vs 0.605, P < 0.001; Akaike Information Criterion, 42141 vs 43118). Regarding the AS, the receipt of PMRT was associated with a better BCSS in those with stage IIIA (P = 0.004), IIIB (P = 0.003), and IIIC (P < 0.001) diseases. Using the PPS, the receipt of PMRT was not associated with a better BCSS among patients with stage IB (P = 0.446), IIA (P = 0.140), and IIB (P = 0.248) disease, while the receipt of PMRT was associated with a better BCSS for those with stage IIIA (P = 0.009), IIIB (P < 0.001), and IIIC (P < 0.001) disease.ConclusionThe 8th AJCC staging provides superior risk stratification and a better tool to predict the benefit of PMRT in N2/3 BC.

Impact of AJCC prognostic staging on prognosis and postmastectomy radiotherapy decision-making in hormone receptor-positive and HER2-positive breast cancer.

BackgroundThe role of postmastectomy radiotherapy (PMRT) in patients with node-positive hormone receptor-positive (HoR) and HER2-positive breast cancer (BC) regarding AJCC pathological prognostic staging (PPS) has not been fully determined. This study aimed to validate PPS in patients with node-positive HoR+/HER2+ BC after mastectomy and to investigate the role of PPS on PMRT decision-making in this patient subset.MethodsPatients diagnosed with BC from the Surveillance, Epidemiology, and End Results database were included. Patients were classified based on the anatomical staging (AS) and PPS. Breast cancer-specific survival (BCSS) was calculated.ResultsIn total, 6862 patients were included: 4306 (62.8 per cent) patients received PMRT and 2556 (37.2 per cent) patients had not. Compared to AS, PPS downstaged 5260 patients (76.7 per cent) and no patients were upstaged. The C-index was similar between PPS and AS (0.690 versus 0.682; P = 0.346). Regarding AS, patients who received PMRT had significantly better BCSS than those who had not in stage IIIA (P = 0.017) and stage IIIC (P < 0.001) disease, but not in stage IB (P = 0.675), IIA (P = 0.677), IIB (P = 0.100), and IIIB (P = 0.747) disease. Regarding PPS, patients who received PMRT had significantly better BCSS than those who had not in stage IIIA (P = 0.038) and stage IIIB (P = 0.017) disease, but not in stage IA (P = 0.336), IB (P = 0.893), IIA (P = 0.815), and IIB (P = 0.120) disease. PPS might allow approximately 1390 stage III patients (45.0 per cent) in the AS criterion to avoid PMRT.ConclusionPPS does not provide better risk discriminatory ability in predicting prognosis than AS in patients with node-positive HoR+/HER2+ BC after mastectomy. However, PPS is valuable in providing prognostic counselling to patients and may also guide PMRT decision-making.

Abstract PD9-01: Expanding downstaging criteria in AJCC pathologic prognostic staging using OncotypeDx Recurrence Score® assay in T1-2N0 hormone-receptor positive patients enrolled in the TAILORx trial

Abstract Background: The AJCC 8th edition pathologic prognostic staging (PPS) system, which incorporates both anatomic and biologic factors, was developed using data from patients captured in the National Cancer Database diagnosed 2010-2012 in whom complete anatomic (T, N and M category) as well as biologic data (grade, ER, PR, HER2) were available. The clinical endpoint was 3-year overall survival. In addition, the use of genomic assays was incorporated based on the initial report from the TAILORx trial, with patients with T1-2N0 hormone-receptor positive, HER2 negative (HR+,HER2-) breast cancer and an Oncotype DX Recurrence Score® (RS) result &amp;lt;11 being staged as PPS IA. Given availability of long-term prospective followup data from TAILORx, we undertook this study to examine if the RS criteria for downstaging to PPS IA can be expanded using the patients enrolled on this trial. Methods: TAILORx assigned T1-2N0 HR+HER2- breast cancer patients with RS &amp;lt;11 to endocrine therapy (ET) alone and RS &amp;gt;25 to chemotherapy followed by ET (CET). Those with RS 11-25 were randomized to ET or CET. 10,273 patients were enrolled. Patients with incomplete HR status or grade and those with T3 disease were excluded for this analysis. Recurrence-free survival (RFS) in patients with RS &amp;lt;11 were compared between patients that did and did not fall into current AJCC PPS IA category using the Kaplan-Meier method. Results: 9,535 patients were included for analysis. The majority were &amp;gt; 50 years old (n=6893, 72.3%), had T1 tumors (n=6561, 68.8%), grade 2 disease (n=5291, 55.5%), and underwent lumpectomy (n=6855, 71.9%). RS breakdown was &amp;lt;11 in 1539 (16.1%), 11-17 in 3423 (35.9%), 18-25 in 3088 (32.4%) and &amp;gt;25 in 1485 (15.6%). 8,698 (91.2%) patients were AJCC PPS IA (including all T1N0 patients regardless of RS), and 837 (8.8%) were not PPS IA. Median follow-up time was 95 months. PPS IA patients had 8-yr RFS of 94.2% which was statistically similar to patients with RS 11-17 that were not PPS IA (91.7%, p=0.07) and better than patients with RS &amp;gt;18 that were not PPS IA (85.4% for RS 18-25, 76.0% for RS &amp;gt;25, p&amp;lt;0.01). For patients with a RS 11-17 that were not PPS IA receiving ET alone, 8-yr RFS was 93.3% which was statistically similar to PPS IA patients receiving ET alone (94.9%, p=0.24). There was no RFS benefit with CET for patients with RS 11-17 not PPS IA (Table). Conclusions: Patients with T1-2N0 HR+HER2- breast cancer and RS&amp;lt;18 have similar RFS to patients staged as PPS IA by the current AJCC staging system, regardless of treatment, suggesting that consideration could be given to expanding the criteria for pathologic prognostic stage IA to include RS&amp;lt;18. Comparison of RFS in patients with Stage IA and not Stage IA by AJCC PPS, n=9535Stage IANot stage IA, RS 11-17Not stage IA, RS 18-25Not stage IA, RS &amp;gt;25All Patients, n=9535n=8698n=169n=269n=3998yr RFS % (95% CI)94.2 (93.6-94.8)91.7 (87.0-96.4)85.4 (80.3-90.5)76.0 (69.1-82.9)P-value*Ref0.07&amp;lt;0.01&amp;lt;0.01ET, n=5370n=5123n=88n=135n=248yr RFS % (95% CI)94.9 (94.1-95.7)93.3 (87.6-99.9)85.1 (77.8-92.4)58.3 (77.8-92.4)P-value*Ref0.24&amp;lt;0.01&amp;lt;0.01CET, n=4165n=3575n=81n=134n=3758yr RFS % (95% CI)93.2 (92.2-94.2)90.0 (82.4-97.6)85.8 (78.7-92.9)76.9 (69.8-84.0)P-value*Ref0.019&amp;lt;0.01&amp;lt;0.01ET endocrine therapy; CET chemoendocrine therapy*compared to T1-2N0 patients with PPS IA Citation Format: Olga Kantor, Harold J Burstein, Tari King, Steven Shak, Christy Russell, Armando E Giuliano, Gabriel N Hortobagyi, Eric P Winer, Larissa A Korde, Joseph A Sparano, Elizabeth A Mittendorf. Expanding downstaging criteria in AJCC pathologic prognostic staging using OncotypeDx Recurrence Score® assay in T1-2N0 hormone-receptor positive patients enrolled in the TAILORx trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-01.

Abstract P3-04-03: The value of screening MRI in patients with high-risk breast lesions: An observational single-institution cohort study

Abstract Background: The value of screening MRI in women with a history of breast atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), collectively termed high-risk lesions (HRL), remains unclear. In our high-risk clinic, we recommend annual mammograms (MMG) and consideration of annual breast MRI, with an emphasis on shared decision-making between patients and providers regarding MRI. Here we report cancer detection rates and outcomes by screening strategy.Methods: Patients with personal history of an HRL evaluated in the Brigham and Women’s Hospital high-risk clinic between 2015-2020 were identified from a prospective database. We excluded those whose HRL upgraded to malignancy at excision, or with a known pathogenic variant in a breast cancer gene. Patient characteristics associated with MRI use were compared with univariable and multivariable logistic regression. Kaplan Meier methods, univariable and multivariable Cox proportional hazards models were used to compare breast cancer detection and biopsy rates during follow-up.Results: Among 914 eligible patients with an HRL, 716 (78%) with at least two clinical visits were included for analysis. Screening MRI was used in 147 (21%) patients; 54% had 1 MRI, 29% had 2 MRIs, and 17% had 3-5 MRIs. Those receiving MRI were significantly younger and more likely to be white, premenopausal, have extremely dense breasts on MMG, normal body mass index, a family member age&amp;lt;50 with breast cancer, LCIS (vs. AH), and higher lifetime breast cancer risk by the Tyrer Cuzick model (all p&amp;lt;0.02). Chemoprevention (CP) was used in 276 (39%) patients and was more common in those receiving MRI (48% vs. 36%, p&amp;lt;0.01). In multivariable analysis, age (OR 0.96, p=0.02), white race (OR 2.98, p&amp;lt;0.01), LCIS (OR 1.72, p=0.03) and CP use (OR 1.68, p=0.01) remained significantly associated with MRI use, with a trend seen for extremely dense breasts (OR 1.6, p=0.07).At a median follow-up of 21 months (IQR: 11-35), 12 (1.7%) patients developed breast cancer, 4 receiving screening MRI and 8 not receiving MRI. The 3-year rate of breast cancer detection was 2.6% (95%CI: 0.8-8.0%) in those with MRI and 2.0% (95%CI: 0.9-5.4%) in those without MRI (p=0.53). Adjusting for age, LCIS vs. AH and CP use, MRI screening was not associated with increased likelihood of cancer detection (HR 1.35, p=0.64). Patients having MRI screening were significantly more likely to require a biopsy during surveillance; 3-year biopsy rates were 24.0% vs. 8.5% (p&amp;lt;0.01).Of the 12 cancers, 3 were DCIS and 8 invasive carcinomas, all clinically node negative, hormone receptor positive and AJCC pathologic prognostic stage 0-I. The remaining 1 cancer was an angiosarcoma. Most of the invasive carcinomas were &amp;lt;2cm (7/8 [88%], median 1.2cm), grade 1-2 (7/8 [88%]), HER2 negative (7/8 [88%]) and pathologic node negative (5/7 [71%] with sentinel node biopsy performed). Of the 4 cancers in those receiving MRI, 50% were visible on MMG. The 2 mammographically occult lesions were 6mm and 2cm MR-detected masses, corresponding to a pT1aN0 invasive tubular carcinoma and a 1.5cm angiosarcoma, respectively.Conclusions: In our high-risk clinic, MRI use was selective, most commonly in women who were younger, white, had LCIS and/or extreme breast density. CP is routinely recommended, yet uptake rates were higher in those receiving MRI, suggesting patient interest in preventative health measures likely also played a role in MRI use. Among patients with an HRL, the 3-year cancer detection rate was 2%, with no difference in rates between those undergoing screening MRI vs. annual MMG alone. However, MRI was associated with a threefold increased risk of breast biopsy. All cancers detected were early stage and clinically node negative. While longer follow-up is needed, the value of MRI screening in patients with HRL appears to be low. Citation Format: Alison Laws, Fisher Katlin, Marybeth Hans, Mary Graichen, Olga Kantor, Christina Minami, Brittany Bychkovsky, Lydia Pace, Rochelle Scheib, Judy Garber, Tari King. The value of screening MRI in patients with high-risk breast lesions: An observational single-institution cohort study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-04-03.

Cumulative Advanced Breast Cancer Risk Prediction Model Developed in a Screening Mammography Population.

Estimating advanced breast cancer risk in women undergoing annual or biennial mammography could identify women who may benefit from less or more intensive screening. We developed an actionable model to predict cumulative 6-year advanced cancer (prognostic pathologic stage II or higher) risk according to screening interval. We included 931 186 women aged 40-74 years in the Breast Cancer Surveillance Consortium undergoing 2 542 382 annual (prior mammogram within 11-18 months) or 752 049 biennial (prior within 19-30 months) screening mammograms. The prediction model includes age, race and ethnicity, body mass index, breast density, family history of breast cancer, and prior breast biopsy subdivided by menopausal status and screening interval. We used fivefold cross-validation to internally validate model performance. We defined higher than 95th percentile as high risk (>0.658%), higher than 75th percentile to 95th or less percentile as intermediate risk (0.380%-0.658%), and 75th or less percentile as low to average risk (<0.380%). Obesity, high breast density, and proliferative disease with atypia were strongly associated with advanced cancer. The model is well calibrated and has an area under the receiver operating characteristics curve of 0.682 (95% confidence interval = 0.670 to 0.694). Based on women's predicted advanced cancer risk under annual and biennial screening, 69.1% had low or average risk regardless of screening interval, 12.4% intermediate risk with biennial screening and average risk with annual screening, and 17.4% intermediate or high risk regardless of screening interval. Most women have low or average advanced cancer risk and can undergo biennial screening. Intermediate-risk women may consider annual screening, and high-risk women may consider supplemental imaging in addition to annual screening.

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.

Coexistence of papillary thyroid carcinoma in secondary hyperparathyroidism

BackgroundThe coexistence of primary hyperparathyroidism and papillary thyroid carcinoma (PTC) is common and may be associative with more aggressive PTC, with higher rates of extrathyroidal extension and multicentricity. However, it is unclear whether secondary hyperparathyroidism (SHPT) is associated with more invasive PTC in terms of morbidity, tumor pathological characteristics, and prognosis. The aim of this study was to evaluate the rate and tumor characteristics of PTC in patients with SHPT.MethodsA total of 531 patients diagnosed with SHPT who underwent surgery from August 2013 to December 2018 at the First Affiliated Hospital of Zhejiang University were evaluated retrospectively. Patient demographics, surgical records, and follow-up information were recorded and analyzed. Control subjects were matched to the enrolled patients in a 1:4 ratio in terms of age, sex and pathological subtype.ResultsAmong the 531 patients with SHPT who underwent surgery, 34 had coexisting PTC and PTC + SHPT (6.4%). The mean tumor diameter in the PTC + SHPT group was smaller than that in the PTC group (5.57 mm vs 9.00 mm, p < 0.001). The proportion of papillary thyroid micro-carcinoma in the PTC + SHPT group was significantly higher than that in the PTC group (29 [85.29%] vs. 86[63.24%], p = 0.014). There were no statistically significant differences between groups in terms of tumor multicentricity (15 [44.12%] vs 39 [28.68%], p = 0.066), tumor bilaterality (9 [26.47%] vs. 29 [21.32%], p = 0.499), tumor extrathyroidal extension (2 [5.88%] vs. 19 [13.97%], p = 0.255), or lymph node (LN) metastasis rate (12 [35.29%] vs. 49 [36.03%], p = 1.000). However, the PTC + SHPT and PTC groups were significantly different in terms of contralateral thyroidectomy (10 [29.41%] vs. 70 [51.47%], p = 0.023) and lymph node dissection (22 [64.71%] vs. 125 [91.91%], p < 0.001).There was no significant difference between the PTC + SHPT and PTC groups in terms of prognostic staging (33 [97.06%] vs. 122 [89.71%], p = 0.309) or recurrence (mean follow-up time: 36 months vs. 39 months, p = 0.33).ConclusionsThe prevalence of PTC is high in patients with SHPT; compared with PTC in the general population, most papillary thyroid carcinomas with SHPT are occult thyroid carcinomas and present no significant difference in terms of tumor pathological features and prognostic staging. It is necessary for surgeons to perform more adequate preoperative examination and be more careful during surgery to avoid missing the coexistence of PTC in patients with SHPT.

Need to restage Korean melanoma patients following publication of the 8th edition of the American Joint Committee on Cancer staging manual.

The tumor, nodes and metastasis (TNM) classification and stage grouping have been updated in the 8th edition of the American Joint Committee on Cancer (AJCC) melanoma staging manual. However, restaging all the previous cases are not recommended. The aims of the study were to investigate the necessity of restaging Korean melanoma patients staged by the previous edition of the AJCC manual. Differences in the staging criteria of the 7th and 8th editions of the AJCC manual were identified. The staging of 276 primary melanomas from January 2011 to December 2018 was classified by both 7th and 8th editions of the manual and their differences were compared. Staging by 7th and 8th edition of the AJCC manual differed in 64 cases (23.2%). The pathological prognostic staging changed in 35 (12.7%), and 29 (10.5%) had changes in only TNM classification but not the pathological staging. None of the patients needed additional sentinel lymph node biopsy or systemic treatment as a result of restaging. Additional counseling was needed for the patients, because melanoma-specific survival was increased in the 8th edition. This is a retrospective study with relatively small number of patients at a single tertiary center in Korea. Assessment of the need for additional sentinel lymph node biopsy or systemic treatment is recommended because of the latest changes in the AJCC melanoma staging manual. Although the restaging of previously staged melanomas is not significantly needed in our patients, still the differences in TNM classification and/or pathological prognostic staging suggest the need to separately recognize the patients previously staged by 7th edition and recently staged by 8th edition. Careful counseling about melanoma-specific survival is needed for Asian patients.

Racial and Socioeconomic Disparities in Breast Cancer Outcomes within the AJCC Pathologic Prognostic Staging System.

Non-Hispanic black (NHB) women and those of lower socioeconomic status (SES) have inferior breast cancer outcomes compared with non-Hispanic white (NHW) women and those of higher SES. We examined racial and SES disparities in breast cancer survival within the AJCC 8th edition pathologic prognostic staging system. Using the Surveillance, Epidemiology and End Results Program, we identified patients diagnosed with invasive breast cancer from 2010 to 2015, with follow-up through 2016. Census tract-level SES (cSES) data were available as a composite index and analyzed in quintiles. Cox proportional-hazards survival analyses adjusted for age, race, cSES, insurance, marital status, histology, pathologic prognostic stage, and treatment were used to estimate disease-specific survival (DSS). A total of 259,852 patients were included: 176,369 (67.9%) NHW; 28,510 (11.0%) NHB; 29,737 (11.4%) Hispanic; and 22,887 (8.8%) Asian. NHB race and lower cSES were associated with increased incidence of triple-negative disease compared with NHW (p<0.01). NHB race, lower cSES, public insurance, lower education, and increased poverty were associated with lower DSS. Survival analyses adjusting for cSES, tumor, and treatment characteristics demonstrated that NHB patients had inferior DSS within each AJCC pathologic prognostic stage (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.20-1.30) compared with NHW patients. Fully adjusted models also showed patients residing in lower SES counties had inferior DSS. Racial and cSES disparities in breast cancer-specific mortality were evident across all stages, even within the pathologic prognostic staging system which incorporates tumor biology. Future efforts should assess the biological, behavioral, social, and environmental determinants that underlie racial and SES inequities in outcomes.

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.

Triple-negative breast cancer outcomes: Does AJCC 8th staging improve chemotherapy decision-making

PurposeTo investigate the effect of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging on chemotherapy decision-making for triple-negative breast cancer (TNBC) patients with T1-2N0M0 disease. MethodsPatients diagnosed with T1-2N0M0 TNBC were retrieved from the Surveillance, Epidemiology, and End Results program. Statistical methods including Kaplan-Meier survival curve, receiver operating characteristics curve, and Cox proportional hazard model. ResultsWe identified 12,156 patients, including 9371 (77.1%) patients who received chemotherapy. Overall, 57.4% of patients (n = 6975) were upstaged after being reassigned by the 8th AJCC staging. However, the 8th staging of AJCC did not have a greater prognostic value compared to the 7th staging (P = 0.064). The receipt of chemotherapy significantly improved the breast cancer-specific survival for stage T1c and T2 tumors (P < 0.001), but not for stage T1a (P = 0.188) and T1b (P = 0.376) tumors. Using AJCC 8th staging, chemotherapy benefit was only found in stage IIA patients (P = 0.002), but not for stage IA (P = 0.653) and IB (P = 0.492) patients. There were 9564 patients with stage T1c and T2 diseases and 4979 patients with 8th AJCC stage IIA disease. Therefore, approximately half of patients (47.9%, n = 4585) may be safe to omit chemotherapy using the AJCC 8th staging compared to the current chemotherapy recommendation for T1-2N0M0 TNBC. ConclusionThe 8th AJCC staging system did not demonstrate the superior discriminatory ability of prognostic stratification than the 7th AJCC staging system in T1-2N0M0 TNBC. However, this new AJCC staging could more accurately predict the chemotherapy benefit, thereby enabling more patients to avoid unnecessary chemotherapy.

Expanding Criteria for Prognostic Stage IA in Hormone Receptor-Positive Breast Cancer.

The prognostic significance of patients with low-risk recurrence score (RS) results in the context of the American Joint Committee on Cancer (AJCC) eighth edition pathologic prognostic staging has not been investigated. We evaluated if expanded RS criteria can be considered for downstaging in AJCC pathologic prognostic staging. Using Surveillance, Epidemiology, and End Results data, we identified patients with T1-3N0-3M0 hormone receptor-positive, HER2-negative breast cancer treated from 2010 to 2015 with follow-up data through 2016. We evaluated TNM categories, grade, and RS result. The primary outcome measured was 5-year disease-specific survival (DSS) of patients with low-risk RS results not already pathologic prognostic stage IA, determined by T and N categories per AJCC eighth edition. All statistical tests were 2-sided. Of 154 050 patients with median follow-up of 49 months (range = 0-83), RS results were obtained in 60 886 (39.5%): RS was less than 11 in 13 570 (22.3%); 11-17 in 22 719 (37.3%); 18-25 in 16 521 (27.1%); and 26 or higher in 8076 (13.3%). Five-year DSS for pathologic prognostic stage IA patients (n = 114 910, 74.6%) was 98.8%. Among N0-1 patients with a RS less than 18 not staged as pathologic prognostic stage IA by current criteria, 5-year DSS was excellent and not statistically significantly different than for pathologic prognostic stage IA patients (97.2%-99.7%; P > .05). For those with a RS of 18-25, there was a small decrease in DSS for T2N0 (2.3%) and modest decrease for T1-2N1 (4.2%-6.4%) compared with pathologic prognostic stage IA patients (P < .001). Patients with a RS less than 18 have excellent 5-year DSS regardless of T category for N0-1 disease suggesting further modification of the AJCC staging system using this cutoff.