A validated model to predict low recurrence risk distinguished by 21-gene recurrence score in hormone receptor-positive invasive breast cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 532-532
Author(s):  
Yasue Tsuchida ◽  
Sachiko Ohde ◽  
Ryota Nakamura ◽  
Yoko Kanada ◽  
Sakiko Miura ◽  
...  

532 Background: In the prospective TAILORx and RxPONDER trials, the 21-gene Recurrence Score (RS) showed endocrine therapy alone was non-inferior to chemo-endocrine therapy in the analysis of invasive disease-free survival in postmenopausal hormone-receptor (HR)-positive breast cancer patients with RS < = 25. They also indicated chemotherapy was associated with benefit for women 50 years or younger with RS 11 to 25. However, in Japan, the test is not conventionally available because of non-coverage by national insurance. We aimed to develop and validate a model to predict RS using clinicopathological factors that identify patients who would have low risk shown by testing the 21-gene RS and can avoid chemotherapy. Methods: Four hundred patients, including 187 N0/1 postmenopausal, and 213 N0 premenopausal women who underwent surgery and had the RS from St. Luke’s International Hospital, Tokyo, Japan, were included in derivation cohort. Derivation cohort was divided into 2 groups by RS 25; patients with RS of 0 to 25 (n = 321) and with RS over 26 (n = 79). Multivariate logistic regression analysis was performed using candidate factors for all patients and pre- or postmenopausal patients. The prediction model was validated using an external cohort of 70 patients from Showa University School of Medicine, Tokyo, Japan. Results: Nuclear grade (NG) (adjusted OR, 5.28, 95% CI, 2.47–11.30), high Progesterone receptor (PgR) expression (Allred score 7-8) (adjusted OR, 10.62, 95% CI, 5.34–21.13) and low Ki67 level ( < = 20%) (adjusted OR, 5.29, 95% CI, 2.33-12.01) were significant independent predictors of RS of 0 to 25. With these factors could predict RS of 0 to 25 (AUC of 0.848, 95% CI, 0.803-0.893) with the highest probability of low-RS for 100%. The prediction model of the validation cohort had same discriminatory ability having an AUC of 0.812 (95% CI, 0.701-0.923). In postmenopausal patients, NG (adjusted OR, 4.81, 95% CI, 1.72–13.42), high PgR expression (adjusted OR, 10.62, 95% CI, 4.52–37.72), and low Ki67 level (adjusted OR, 4.94, 95%CI, 1.87-13.04) were significantly associated with RS of 0 to 25 in multivariate analysis. A regression model with these 4 factors could predict RS of 0 to 25 (AUC of 0.842, 95%CI, 0.782-0.902). In premenopausal patients, NG (adjusted OR, 8.76, 95% CI, 1.14–67.40), high PgR expression (adjusted OR, 3.22, 95% CI, 1.61–6.43), and low Ki67 level (adjusted OR, 2.87, 95% CI, 1.20–6.87) were significantly associated with RS of 0 to 10 in multivariate analysis. These factors could predict RS of 0 to 10 (AUC of 0.811, 95% CI, 0.731-0.891). However, the highest probability of low-RS provided this model for premenopausal women was 46.8%. Conclusions: Our validated model could provide useful information to distinguish low-RS especially for postmenopausal patients with high reproducibility. However, for premenopausal women, the 21-gene RS is warranted.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22065-e22065 ◽  
Author(s):  
R. Wesolowski ◽  
A. G. Shealy ◽  
J. Tao ◽  
H. C. Moore

e22065 Background: Mutations in BRCA1 and BRCA2 genes lead to defects in DNA repair. Estrogen receptor modulates transcription of genes responsible for cell division, which depends on cell's ability to repair DNA for genomic integrity. Differential efficacy of endocrine therapy for breast cancer, therefore, may be possible depending on the tumor's BRCA mutation status. Methods: Through an IRB approved registry, breast cancer patients tested for BRCA1 and BRCA2 mutations and treated with endocrine therapy for hormone-receptor positive non-metastatic disease were identified. Primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS) respectively. Fisher's exact test or Wilcoxon rank sum test were used to assess differences among subgroups with respect to their characteristics. Cox proportional hazard analysis was used to identify univariate and multivariate risk factors for OS and PFS. Results: Of 115 breast cancer patients tested for BRCA mutations, 63 met the inclusion criteria of whom 16 patients were BRCA 1 or 2 mutation positive and 47 were negative. In the BRCA(+) group, 14 patients (87.5%) had stage I-III disease at diagnosis. In the BRCA(-) group, 5 patients (10.6%) had stage 0 disease while 41 patients (87.2%) had stage I-III disease at diagnosis. Stage at diagnosis was unavailable for 2 BRCA(+) and 1 BRCA(-) patients. Both groups were similar with respect to Her-2 expression status, history of ovarian suppression, age of diagnosis, and age of menopause. Median age was 48 yo in BRCA(+) group, 42 yo in BRCA(-), (p=0.12). Median follow up was 76.1 mos in BRCA(+) and 62.9 mos in BRCA(-) group. OS was worse in BRCA(+) group (HR 7.38, 95% [CI] 1.49–36.4 p=0.014). After adjustment for stage and history of ovarian suppression, the difference remained significant (HR 16.6, 95% [CI] 1.95–142, p=0.010). There was no difference in PFS (HR 2.02, 95% [CI] 0.82–4.96, p=0.13). Conclusions: Patients with BRCA mutation, hormone-receptor positive hereditary breast cancer treated with endocrine therapy had inferior survival compared with similar patients who are BRCA mutation negative. Prospective studies to evaluate the differential effects of endocrine therapy in these populations are warranted. No significant financial relationships to disclose.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12014-e12014
Author(s):  
Sowmya Goranta ◽  
Tarek Haykal ◽  
Areeg Bala ◽  
Ragheed Al-Dulaimi ◽  
Ghassan Bachuwa ◽  
...  

e12014 Background: Oncotype-DX Assay is a 21-gene based recurrence score (RS) that helps stratify breast cancer patients based on their risk of recurrence. It is often used to help identify patients that may benefit from adjuvant chemotherapy (AC). Prior to the TAILORx Trial results, there were no guidelines for AC in patients with an intermediate score (18-30). Management of these patients was often at the clinical judgement of the provider. We sought to determine predictors of AC among these patients, and measure treatment effect on survival. Methods: We queried the Surveillance, Epidemiology, and End-Results database for breast cancer patients newly diagnosed between 2010-2015. We included patients with T1-T3, hormone receptor positive, HER2-negative, and lymph node-negative breast cancer with an intermediate RS. Male patients, those younger than 40 years, tumors 5 mm or less, and incomplete records were excluded. Univariate and multivariate analysis was performed to derive independent predictors of AC. Cox Proportional-Hazards Model was done to examine the effect of AC on survival. Results: We included 14,710 patients of whom 4,508 (30.6%) received AC. Patients that received AC were younger (55.4 years [8.8] vs 60.0 [9.7], p < 0.001), grade III or higher (29.8% vs 16.4%, p < 0.001), and had a higher RS (23.9 [3.6] vs 21.5 [3.1], p < 0.001). Higher T stage was associated with a higher rate of patients receiving AC (p < 0.001). Marital status was also associated with AC; a higher proportion of patients who received AC were married (67.9% vs 64.4%, p < 0.001). There was no significant association between race/ethnicity or insurance type with AC. Multivariate analysis showed that RS (OR: 1.24 [1.23-1.26], p < 0.001), T stage (OR: 1.67 [1.21-2.30], p < 0.001), and a grade III tumor (OR: 1.85 [1.64-2.09], p < 0.001) were the strongest predictors of AC. The age decile 80-89 years (OR: 0.05 [0.02-0.10], p < 0.001) was the most negative predictor of AC. AC did not have an effect on 5 year overall survival (97.6% vs 96.0%, p = 0.28). Conclusions: Between 2010-2015, our study shows 30.6% of breast cancers patients with an intermediate Oncotype-DX score were given AC. The decision to treat was largely based on tumor size, grade and age. AC had no effect on overall survival.


2014 ◽  
Vol 50 (13) ◽  
pp. 2190-2200 ◽  
Author(s):  
Duveken B.Y. Fontein ◽  
Ayoub Charehbili ◽  
Johan W.R. Nortier ◽  
Elma Meershoek-Klein Kranenbarg ◽  
Judith R. Kroep ◽  
...  

Breast Cancer ◽  
2012 ◽  
Vol 21 (5) ◽  
pp. 557-562 ◽  
Author(s):  
Daisuke Shimizu ◽  
Takashi Ishikawa ◽  
Mikiko Tanabe ◽  
Takeshi Sasaki ◽  
Yasushi Ichikawa ◽  
...  

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hsu-Huan Chou ◽  
Wei-Shan Chung ◽  
Rong-Yao Ding ◽  
Wen-Ling Kuo ◽  
Chi-Chang Yu ◽  
...  

Abstract Background Neoadjuvant chemotherapy (NAC) has been the standard treatment for locally advanced breast cancer for the purpose of downstaging or for conversion from mastectomy to breast conservation surgery (BCS). Locoregional recurrence (LRR) rate is still high after NAC. The aim of this study was to determine predictive factors for LRR in breast cancer patients in association with the operation types after NAC. Methods Between 2005 and 2017, 1047 breast cancer patients underwent BCS or mastectomy after NAC in Chang Gung Memorial Hospital, Linkou. We obtained data regarding patient and tumor characteristics, chemotherapy regimens, clinical tumor response, tumor subtypes and pathological complete response (pCR), type of surgery, and recurrence. Results The median follow-up time was 59.2 months (range 3.13–186.75 months). The mean initial tumor size was 4.89 cm (SD ± 2.95 cm). Of the 1047 NAC patients, 232 (22.2%) achieved pCR. The BCS and mastectomy rates were 41.3% and 58.7%, respectively. One hundred four patients developed LRR (9.9%). Comparing between patients who underwent BCS and those who underwent mastectomy revealed no significant difference in the overall LRR rate of the two groups, 8.8% in BCS group vs 10.7% in mastectomy group (p = 0.303). Multivariate analysis indicated that independent factors for the prediction of LRR included clinical N2 status, negative estrogen receptor (ER), and failure to achieve pCR. In subgroups of multivariate analysis, only negative ER was the independent factor to predict LRR in mastectomy group (p = 0.025) and hormone receptor negative/human epidermal growth factor receptor 2 positive (HR−/HER2 +) subtype (p = 0.006) was an independent factor to predict LRR in BCS patients. Further investigation according to the molecular subtype showed that following BCS, non-pCR group had significantly increased LRR compared with the pCR group, in HR−/HER2 + subtype (25.0% vs 8.3%, p = 0.037), and HR−/HER2− subtype (20.4% vs 0%, p = 0.002). Conclusion Clinical N2 status, negative ER, and failure to achieve pCR after NAC were independently related to the risk of developing LRR. Operation type did not impact on the LRR. In addition, the LRR rate was higher in non-pCR hormone receptor-negative patients undergoing BCS comparing with pCR patients.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1054-1054 ◽  
Author(s):  
Ajay Dhakal ◽  
Christina Matthews ◽  
Fan Zhang ◽  
Ellis Glenn Levine ◽  
Stephen B. Edge ◽  
...  

1054 Background: Resistance mechanisms to CDK 4/6 inhibition are not well defined. Outcome data on hormone receptor positive (HR+) metastatic breast cancer patients (MBCP) treated with palbociclib (PA) after treatment with everolimus (EV) are lacking. The PALOMA 3 trial (P3) showing benefit of PA plus fulvestrant (FU) compared to FU in HR+ MBCP after progression on endocrine therapy excluded women previously treated with EV. The aim of our study was to investigate the outcomes of HR+ MBCP with prior EV treatment on PA based therapy. Methods: This is a retrospective, single institute review of HR+, HER 2 nonamplified MBCP from Jan 2014 - Nov 2016 treated with PA after treatment with EV. Women who received EV for < 1 month or PA < 14 days were excluded. Progression free survival (PFS) was defined as the time from the initiation of PA to the date of progression as determined by treating physician based on radiological, biochemical and/or clinical criteria. Response rates were determined based on available radiological data. Clinical benefit was defined as a complete response (CR), partial response (PR) or stable disease of at least 24 weeks. Results: 23 patients with mean age 67 years (42 to 81) were identified. 95% were postmenopausal, 81% had ECOG performance status 0 or 1, 83% had visceral metastases, 95% had > 2 lines of prior endocrine therapy (ET), 82% shown prior sensitivity to ET, 82% received prior chemotherapy, of which 84% were in metastatic setting. Kaplan Meier estimate showed median PFS of 2.9 months (95% CI 2.0-4.2); median PFS of P3 PA cohort was 9.5 months (95% CI 9.2-11.0). Fisher’s exact test comparing study cohort with P3 PA cohort showed statistically significant differences in objective response (CR or PR) rates of 0/23 (0%) vs. 66/347 (19%, p = 0.02) & clinical benefit ratio of 4/23 (17.4%) vs. 231/347 (66.5%, p = 0.00). Conclusions: Outcomes with PA in HR+ EV treated MBCP were worse when compared to the P3 PA cohort data. Treatment with EV may lead to resistance to CDK inhibition. Though limited by size, our data suggests that use of PA after EV is associated with low response & clinical benefit rates. Further studies are necessary to confirm the findings to determine sequencing of targeted therapies.


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