5-year Breast Cancer-specific Survival Research Articles

Impact of Breast Cancer Subtypes on Prognosis of Women with Operable Invasive Breast Cancer: A Population-based Study Using SEER Database.

To determine the prognostic roles of breast cancer subtypes in females with operable invasive breast cancer.Experimental Design: Data of 321,958 patients from Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Breast cancer subtypes were classified into four categories according to the status of hormone receptor (HRc) and HER2: HRc(+)/HER2(-), HRc(+)/HER2(+), HRc(-)/HER2(+), and HRc(-)/HER2(-). Proportions of HRc(+)/HER2(-), HRc(+)/HER2(+), HRc(-)/HER2(+), HRc(-)/HER2(-), and unknown subtype were 70.3%, 9.4%, 3.9%, 10.4%, and 6.0%, respectively. HRc(+)/HER2(-) showed the highest 5-year breast cancer-specific survival (BCSS) rate (95.5%), followed by HRc(+)/HER2(+) (94.1%), HRc(-)/HER2(+) (89.3%), and HRc(-)/HER2(-) (83.1%). HRc(+)/HER2(-) and HRc(+)/HER2(+) showed higher 5-year overall survival (OS) rates (88.4% and 88.2%, respectively) than HRc(-)/HER2(+) and HRc(-)/HER2(-) (83.9% and 76.5%, respectively). HRc(-)/HER2(-) showed the worst BCSS irrespective of race, age, or stage. Although proportions of HRc(-)/HER2(-) in the subgroup with negative event regarding BCSS and OS were 10.4% and 10.2%, respectively, they were 34.2% and 22.7%, respectively, in the subgroup with positive event. Subtype was a significant factor in both univariable and multivariable analyses regarding both BCSS and OS (all P < 0.001). Breast cancer subtype was a significant independent prognostic factor regarding both BCSS and OS in multivariable analyses. HRc(+) subtypes showed better prognosis compared with HRc(-) subtypes regarding both BCSS and OS. HRc(-)/HER2(+) showed better prognosis than HRc(-)/HER2(-) but worse prognosis than HRc(+) subtypes regarding both BCSS and OS. The triple-negative subtype showed the worst BCSS compared with the other subtypes irrespective of race, age, or stage.

Noninferior Outcome After Breast-Conserving Treatment Compared to Mastectomy in Breast Cancer Patients With Four or More Positive Lymph Nodes.

Introduction: We conducted a non-inferiority analysis using real-world data to compare the survival outcomes of stage T1-2N2-3 (tumor size ≤5 cm and four or more node metastases) breast cancer after breast-conserving surgery (BCS) and mastectomy (MAST).Methods: The study included patients with stage T1-2N2-3 invasive breast carcinoma from the Surveillance, Epidemiology, and End Results program, who underwent BCS or MAST between 2004 and 2012, along with both radiotherapy and chemotherapy. The statistical analyses used included the chi-squared test, multivariate Cox proportional hazards models, and propensity score matching (PSM).Results: The study population comprised 13,263 patients, including 4,787 (36.1%) and 8,476 (63.9%) patients who were treated with BCS and MAST, respectively. Patients with younger age and advanced stage were more likely to have received MAST. The probability of receiving MAST increased over the years, while the probability of BCS decreased (p < 0.001). The 5-year breast cancer-specific survival (BCSS) was 86.1% in the BCS cohort compared to 83.1% in the MAST cohort (p < 0.001). Surgical procedure was an independent prognostic factor for BCSS. Patients who received MAST had worse BCSS than those treated with BCS (hazard ratio = 1.179, 95% confidence interval = 1.087–1.278, p < 0.001). These results remained significant after stratification by age, tumor grade, T stage, N stage as well as marital status. Similar results were obtained after PSM.Conclusions: BCS resulted in noninferior outcome than MAST in patients with T1-2/N2-3 invasive breast carcinoma. BCS may therefore be an optimal treatment option when both treatment options are feasible and appropriate.

Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases.

PurposeThe purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC).MethodsPatients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed.ResultsWe identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs.ConclusionThe 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.

Survival outcome of adjuvant endocrine therapy alone for patients with lymph node-positive, hormone-responsive, HER2-negative breast cancer

The prognosis of hormone receptor-positive and HER2-negative breast cancer is better than that of other subtypes. Current guidelines recommend chemotherapy for N1 breast cancer patients. However, this has the possibility to be over-treatment. This was a retrospective study of 18,549 patients who were surgically treated for invasive breast cancer, at a single center in South Korea, between January 1993 and December 2012. N1 stage breast cancer patients who were hormone receptor-positive and HER2-negative were enrolled, and propensity score matching was performed to compare patients treated with anti-hormonal therapy alone (N=83) and those treated with chemotherapy followed by anti-hormonal therapy (N=85). In survival analysis, the survival parameters of the endocrine therapy-only group and the chemotherapy with endocrine therapy group were respectively 96.1% and 94.0% for 5-year recurrence free survival (RFS), 89.6% and 94.0% for 10-year RFS, 97.4% and 94.0% for 5-year distant metastasis-free survival (DMFS), 93.2% and 94.0% for 10-year DMFS, 98.7% and 98.8% for 10-year breast cancer-specific survival (BCSS), and 98.7% and 98.8% for 10-year overall survival (OS). There were no significant differences in RFS (p=0.871), DMFS (p=0.491), BCSS (p=0.569) and OS (p=0.731) between the two groups. Several patients with clinicopathologic features like hormone receptor positivity and HER2 negativity can avoid chemotherapy even with lymph node metastasis. Future studies with a long-term follow-up and a larger number of patients are required for validating our results.

Abstract P4-08-01: Is the 8th edition of the breast cancer TNM staging system an improvement over the 7th edition?

Abstract Background: The revised 8th edition of the TNM staging system was published on January 25, 2018 (https://cancerstaging.org/references-tools/deskreferences/Pages/Breast-Cancer-Staging.aspx). The new prognostic staging system (PrSS) was developed using the outcomes of 334,243 patients from the National Cancer Database (NCDB) with a median follow-up of 3.5 years after treatment in 2010-2012. The PrSS was created by clustering patients by outcome into the eight sub-stages of the 7th edition TNM anatomic staging system (AnSS) using more than 169 combinations of stage, ER, PR, H2, grade and molecular test results. This study aimed to assess the prognostic performance of the PrSS in an independent cohort with longer follow-up. Methods: The Breast Cancer Unit Outcomes database was used to identify patients treated without neoadjuvant systemic therapy in 2005-2014, when use of anti-Her2 therapies was routine. Ten-year breast cancer-specific survival (BCSS) was determined using the Kaplan-Meier method. Using age, ER, PR, H2, grade, chemotherapy, type of surgery and radiotherapy variables for the AnSS and the same variables minus ER, PR, H2, and grade, which are built into the PrSS, Harrell's c-indices were calculated to compare the predictive performance of the AnSS and PrSS models (higher quality models have higher c-indices). Results: The study cohort had 19,581 patients with a median follow-up of 7.3 years. Relative to the AnSS, 5.2% (1009/19,581) had higher prognostic stages and 36.5% (7,149/19,581) had lower prognostic stages. The c-indices were 0.83 for the AnSS and 0.81 for the PrSS. Overlapping 10-year BCSS confidence intervals (CI) were observed for stages IIIB and IIIC, which contained few patients in both staging systems. There were also overlapping CIs for two other anatomic stages: IA &amp; IB and four other prognostic stages: IB &amp; IIA and IIB &amp; IIIA. Comparison of Anatomic and Prognostic TNM Staging Number of Patients10-year BCSSStagesAnatomicPrognosticAnatomic (%) (CI)Prognostic (%) (CI)IA9,19511,98796.4 (95.8, 96.9)95.9 (95.4, 96.4)IB6083,01595.1 (92.2, 96.9)86.7 (84.9, 88.3)IIA4,8402,03889.9 (88.7, 91.0)85.4 (83.4, 87.1)IIB2,49586983.9 (81.9, 85.7)73.9 (70.0, 77.4)IIIA1,54978975.0 (72.0, 77.6)70.8 (66.7, 74.5)IIIB9435754.8 (40.3, 67.2)57.1 (50.4, 63.2)IIIC53926553.0 (47.6, 58.1)50.8 (43.7, 57.4)IV26126123.8 (17.6, 30.5)23.8 (17.6, 30.5) Conclusions: For 10-year BCSS, the c-index was higher for the AnSS than for the PrSS. In addition, more statistically distinct stages were observed for the AnSS than the PrSS. The increased complexity of the PrSS did not appear to provide better prognostication than the AnSS in our large series with longer follow-up than the NCDB. Citation Format: Nichol AM, Lohrisch CA, Gondara L, Speers CH, Gelmon KA. Is the 8th edition of the breast cancer TNM staging system an improvement over the 7th edition? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-01.

Abstract P2-07-12: A prognostic prediction nomogram (PDIDC) for breast Paget's disease with infiltrating ductal carcinoma patients: A SEER cohort analysis

Abstract Purpose The aim of the study was to develop a specific nomogram for prediction of prognosis for breast Paget's disease with infiltrating ductal carcinoma (PD-IDC) patients. Patients and Methods Patients data were obtained by the Surveillance, Epidemiology, and End Results (SEER) program (N=2502). Study outcome was Breast Cancer Specific Survival (BCSS). Cox proportional hazards model was applied to identify risk factors and develop predictive model. For internal validation, discrimination was calculated with the concordance index (C-index) using the bootstrap method and calibration assessed. Results NPI classification, skin symptom, tumor site and age showed significant association with BCSS(table.1)and were used to build the PDIDC nomogram and to calculate risk score. PDIDC nomogram's C-index (0.791, 95%CI 0.783-0.818) showed better discrimination power than NPI classification (0.691, 95%CI, 0.650-0.735, P= 0.000) and AJCC staging (0.718, 95%CI, 0.695-0.741, P=0.000). Patients were divided into high-risk (1882/2502, 75.21%) and low-risk (620/2502, 24.78%) subgroups with the optimal cut-off of risk scores (4.28). The total BCSS of low-risk subgroup was 77.8% (95%CI 74.4%-81.4%) vs. 31.1% (95%CI 19.4-49.8) of high-risk group (P=0.000). Bootstrap internal validation demonstrated an average C-index of 0.739 (95% CI, 0.692-0.746). The nomogram calibration was validated to be accurate in predicting 5-year and 10-year survival. Variable finally selected for risk predicted model.PredictorHazard RatioP Value95% CINPI classification Good1 Moderate2.170.0001.51-3.14Poor7.260.0004.96-10.63Skin symptom Without1 With1.760.0001.34-2.32Tumor site Centrally located1 Non-centrally located1.250.0421.07-1.56Age*1.010.0001.01-1.03* Continuous variable. Conclusion Utilizing NPI classification, skin symptom, tumor site and age, we developed the PDIDC nomogram to predict the 5-year and 10-year BCSS of breast PD-IDC patients. Citation Format: Tan L, Chen K, Jiang WG, You N, Wang Y, Sanders A, Liang G, Liu Z, Ling Y, Zhong W, Tian Z, Gong C. A prognostic prediction nomogram (PDIDC) for breast Paget's disease with infiltrating ductal carcinoma patients: A SEER cohort analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-12.

The Role of Axillary Lymph Node Dissection in Tubular Carcinoma of the Breast: A Population Database Study.

BackgroundThe aim of this study was to investigate the role of axillary lymph node dissection on the outcome of patients with tubular carcinoma of the breast.Material/MethodsPatients diagnosed with tubular carcinoma of the breast between 2000–2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analysis of the data was undertaken, including analysis of breast cancer-specific survival (BCSS).ResultsOf the 5,645 patients identified on the SEER database with tubular carcinoma of the breast, 5,032 (89.4%) patients had undergone axillary lymph node dissection, with significantly increased rates after 2002 compared with rates between 2000–2001 (p <0.001), which stabilized between 2002–2013 (p=0.330). Axillary lymph node metastases were present in 6.1% of all patients and in 5.3% of patients with a tumor size ≤2 cm. Lymph node-positive disease was associated with patient age ≤65 years, intermediate-grade or high-grade tumors, and tumor size >2.0 cm. Axillary lymph node dissection was an independent prognostic indicator. The 10-year BCSS was 97.3% and 96.6% in patients with and without axillary lymph node dissection, respectively (p=0.002). The number of removed lymph nodes was not related to breast cancer-specific survival.ConclusionsIn patients with tubular carcinoma of the breast, lymph node status was not associated with significant breast cancer-specific survival. However, axillary lymph node dissection may still be considered for patients with for tubular carcinoma of the breast even in patients with a small tumor size.

Liver Kinase B1-A Potential Therapeutic Target in Hormone-Sensitive Breast Cancer in Older Women.

Background: The role of liver kinase B1 (LKB1), a serine/threonine kinase, has been described in the development of PeutzJagher’s syndrome, where a proportion (~45%) of patients have developed breast cancer in their lifetime. Cell line studies have linked LKB1 with oestrogen receptors (ER) and with the Adenosine monophosphate-activated protein kinase (AMPK) pathway for energy metabolism. However, limited studies have investigated protein expression of LKB1 in tumour tissues and its intracellular relationships. This study aimed to investigate the intracellular molecular relationships of LKB1 in older women with early operable primary breast cancer and its correlation with long-term clinical outcome. Methods: Between 1973 and 2010, a consecutive series of 1758 older (≥70 years) women with T0-2N0-1M0 breast carcinoma were managed in a dedicated facility. Of these, 813 patients underwent primary surgery, and 575 had good quality tumour samples available for tissue microarray construction. LKB1 was assessed in 407 cases by indirect immunohistochemistry (IHC). Tumours with 30% or more of cells with cytoplasmic LKB1 expression were considered positive. LKB1 expression was compared with tumour size, histological grade, axillary lymph node stage, ER, PgR, EGFR, HER2, HER3, HER4, BRCA1&2, p53, Ki67, Bcl2, Muc1, E-Cadherin, CD44, basal (CK5, CK5/6, CK14 and CK17) and luminal (CK7/8, CK18 and CK19) cytokeratins, MDM2 and MDM4, and correlated with long-term clinical outcome. Results: Positive LKB1 expression was seen in 318 (78.1%) patients, and was significantly associated with high tumour grade, high Ki67, over-expression of HER2, VEGF, HER4, BRCA2, MDM2 and negative expression of CD44 (p < 0.05). There was no significant correlation with tumour size, axillary lymph node status, ER, PgR, p53, basal or luminal cytokeratins, Bcl2, Muc1, EGFR, HER3, MDM4, E-cadherin and BRCA1. LKB1 did not show any significant influence on survival in the overall population; however, in those patients receiving adjuvant endocrine therapy for ER positive tumours, those with positive LKB1 had significantly better 5-year breast cancer specific survival when compared to those without such expression (93% versus 74%, p = 0.03). Conclusion: LKB1 expression has shown association with poor prognostic factors in older women with breast cancer. However, LKB1 expression appears to be associated with better survival outcome among those patients receiving adjuvant endocrine therapy. Further research is required to explore its potential role as a therapeutic target.

Comparative Analysis of Outcomes and Clinicopathological Characteristics of Synchronous and Metachronous Contralateral Breast Cancer: A Study of the SEER Database.

PurposeNumerous previous studies have reported inconsistent results about the differences between synchronous contralateral breast cancer (sCBC) and metachronous contralateral breast cancer (mCBC). This study aimed to compare the clinical characteristics and outcomes between sCBC and mCBC and determine predictive factors for the survival of sCBC and mCBC patients.MethodsUsing the Surveillance, Epidemiology, and End Results Program database, we identified sCBC or mCBC patients from 2000 to 2010. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to analyze overall survival and breast cancer-specific survival (BCSS) rates of sCBCs and mCBCs, respectively.ResultsOverall, 14,057 sCBC (n = 8,139, 57.9%) and mCBC (n = 5,918, 42.1%) patients were included. The first tumors of sCBC were more likely to have higher stage and more lymph and distant metastases, whereas those of mCBC were more often infiltrating ductal carcinoma (IDC), had localized stage, were estrogen receptor (ER) and progesterone receptor (PR) negative, and had less axillary nodal involvement. The second tumors of mCBC tended to be IDC and have higher grade, adverse stage, ER and PR-negativity; and more axillary nodal involvement, compared to the second tumors of sCBC. mCBC patients had significantly favorable 5-year BCSS but worse long-term BCSS compared with sCBC patients. Moreover, subgroup analysis revealed no significant difference of BCSS between sCBC and mCBC among patients aged 18–60 years. Multivariate analysis indicated that age, grade, and stage of 2 tumors; surgery for second tumor; and ER status of the second tumor were independent prognostic factors for BCSS of contralateral breast cancer (CBC).ConclusionThe characteristics and outcomes of sCBCs and mCBCs were substantially different. sCBC and mCBC patients may have different prognosis, and the prognosis of CBC depends on the first and second tumors.

Predictors for Survival and Distribution of 21-Gene Recurrence Score in Patients With Pure Mucinous Breast Cancer: A SEER Population-Based Retrospective Analysis

BackgroundPure mucinous breast cancer (PMBC) is a rare pathologic type of breast cancer, the prognostic factors of which have not been clearly defined. This study aimed to analyze the prognostic markers and distribution of 21-gene recurrence score (RS) in patients with PMBC. Patients and MethodsUtilizing the Surveillance, Epidemiology, and End Results (SEER) database, a retrospective analysis of PMBC cases was conducted. Multivariate analyses were used to evaluate the indicators for prognosis and the correlations between RS and traditional clinicopathologic characteristics. Disease was subdivided into 4 molecular phenotypes using estrogen receptor (ER) status and tumor grade. ResultsOf the 8048 patients, most had ER-positive and node-negative tumors. Multivariate analysis revealed that molecular phenotype as well as age, race, tumor size, and lymph node status was an independent prognostic factor for patients with PMBC (P < .05). The 5-year breast cancer–specific survival of patients among different phenotypes was significantly different (97.9% for ER-positive and grade I tumor, 96.9% for ER-positive and grade II-III tumor, 96% for ER-negative and grade I tumor, 90.1% for ER-negative and grade II-III tumors, P < .001). The proportions of patients categorized into low, intermediate, and high RS risk group were 64.9%, 31.9%, and 3.2%, respectively. Grade, progesterone receptor status, and age were identified as independent variables associated with RS. ConclusionPMBC had favorable biological features and relatively good prognosis. Molecular phenotype as well as age, race, tumor size, and lymph node status were independent prognostic markers. Furthermore, age, progesterone receptor status, and grade could independently predict RS.

Influence of Age on the Clinical Outcome of Breast Cancer for Men and the Development of Second Primary Cancers.

Low incidence of breast cancer in men (BCM) (< 1% of all breast cancers) has led to a paucity of outcome data. This study evaluated the impact of age on BCM outcomes. For this study, BCM patients treated between 2000 and 2011 were stratified by age (≤ 65 or > 65years). Kaplan-Meier methods were used to compare overall survival (OS) and breast cancer-specific survival (BCSS). Competing-risk methods analyzed time to second primary cancers (SPCs), with any-cause death treated as a competing risk. The study identified 152 BCM patients with a median age of 64years (range 19-96years). The median body mass index (BMI) was 28kg/m2. Men age 65years or younger (n = 78, 51%) were more overweight/obese than men older than 65years (n = 74, 49%) (89% vs 74%, respectively; P = 0.008). Both groups had similar nodal metastases rates (P = 0.4), estrogen receptor positivity (P = 1), and human epidermal growth factor receptor 2 (HER2)neu overexpression (P = 0.6). Men 65years of age or younger were more likely to receive chemotherapy (P = 0.002). The median follow-up period was 5.8years (range 0.1-14.4years). The 5-year OS was 86% (95% confidence interval [CI] 80-93%), whereas the 5-year BCSS was 95% (95% CI 91-99%). The BCM patients 65years of age and younger had better OS (P = 0.003) but not BCSS (P = 0.8). The 5-year cumulative incidence of SPC was 8.4% (95% CI 3.4-13.4%). The prior SPC rate was higher for men older than 65years (n = 20, 31%) than for those age 65years or younger (n = 7, 11%) (P = 0.008). This did not account for differences in life years at risk. No difference was observed in SPC cumulative incidence stratified by age (P = 0.3). Men 65years of age or younger received more chemotherapy and had improved OS, but not BCSS, compared with men older than 65years. For all BCM, SPC is a risk, and appropriate screening may be warranted.

A New Predictive Model for Breast Cancer Survival in New Zealand: Development, Internal and External Validation, and Comparison With the Nottingham Prognostic Index

Background: Women diagnosed with breast cancer, their doctors, and their families, would find a valid estimate of her prognosis helpful in planning treatment and support. Assessing prognosis is complex as many factors influence it. Several predictive models have been produced, but none has been developed or tested on patients in New Zealand (NZ). Aim: We aimed to develop and validate a NZ predictive model (NZPM) for breast cancer, and compare its performance to a widely used UK-developed model, the Nottingham Prognostic Index (NPI). Methods: We developed a model to predict 10-year breast cancer-specific survival, using data collected prospectively in the largest population-based breast cancer registry in NZ (Auckland, 9182 patients), and assessed its performance in this data set (internal validation) and in an independent NZ population-based series of 2625 patients in Waikato (external validation). The data included all women with primary invasive breast cancer diagnosed from 1 June 2000 to 30 June 2014, with follow-up to death or to 31 December 2014. We used multivariate Cox proportional hazards regression to assess predictors and to estimate the probability of breast cancer mortality within 10 years, and therefore 10-year survival, for each patient. We assessed observed survival by the Kaplan-Meier method. We assessed discrimination by the C-statistic, and calibration by comparing predicted and observed survival rates for patients in 10 groups ordered by predicted 10-year survival. We compared this NZPM with the NPI in the validation data set. Results: The final NZPM used continuous variables of age, tumor size, and number of positive lymph nodes, and categorical variables of ethnicity, tumor stage, tumor grade, ER and PR receptors, HER2 status, and histologic type of tumor. Discrimination was good: C-statistics were 0.84 for internal validity and 0.83 for independent external validity. For calibration, for both internal and external validity, the predicted 10-year survival probabilities in 10 groups of patients, ordered by predicted survival, were all within the 95% confidence intervals (CI) of the observed Kaplan-Meier survival probabilities. The NZPM showed good discrimination even within the prognostic groups defined by the NPI. Conclusion: These results for the NZPM show good internal and external validity, transportability, potential clinical value, and its clear superiority over the NPI. Further research will assess other potential predictors, other outcomes, performance in specific subgroups of patients, and compare the NZPM to other models, which have been developed in other countries and have not yet been tested in NZ.

Clinicopathologic characteristics and clinical outcomes of pure type and mixed type of tubular carcinoma of the breast: a single-institution cohort study.

IntroductionWe aimed to evaluate the clinicopathologic characteristics and clinical outcomes of the mixed type versus the pure type of tubular carcinoma (TC) of the breast in a retrospective cohort study.Materials and methodsPatients were categorized into the following three groups: patients with pure TC of the breast (the PTC group), patients with TC and carcinoma in situ of the breast (the TC-CIS group), and patients with TC and other invasive carcinomas of the breast (the TC-IC group). We compared the clinicopathologic characteristics and treatment outcomes of the three groups. The primary end point of this study was breast cancer-specific survival (BCSS). Secondary end points included distant metastasis-free survival (DMFS) and locoregional recurrence (LRR).ResultsA total of 68 patients were included in this study, including 31 patients in the PTC group, 12 in the TC-CIS group, and 25 in the TC-IC group. Our data showed that PTC and TC-CIS were more likely to be smaller in size (P=0.014) and had substantially less nodal involvement (P=0.019), compared with TC-IC. The median follow-up time was 64.3 months (range, 3.78–223.2 months) for all patients. No locoregional relapse was observed in any group during the follow-up period. The 10-year BCSS of the PTC, TC-CIS, and TC-IC groups was 100%, 100%, and 95.2%, respectively, and the 10-year DMFS was 92.3%, 100%, and 96.0%, respectively. There was no significant difference in terms of BCSS (P=0.53) or DMFS (P=0.84) between the three groups.ConclusionThis study indicates that both the pure type and mixed type of TC of the breast show very low LRR and distant metastasis rate and have excellent survival. The TC-IC group is likely to show good prognosis similar to the PTC group. Further clinical trials with larger sample sizes as well as molecular and genetic studies are warranted.

Development and validation of a new predictive model for breast cancer survival in New Zealand and comparison to the Nottingham prognostic index

BackgroundThe only available predictive models for the outcome of breast cancer patients in New Zealand (NZ) are based on data in other countries. We aimed to develop and validate a predictive model using NZ data for this population, and compare its performance to a widely used overseas model, the Nottingham Prognostic Index (NPI).MethodsWe developed a model to predict 10-year breast cancer-specific survival, using data collected prospectively in the largest population-based regional breast cancer registry in NZ (Auckland, 9182 patients), and assessed its performance in this data set (internal validation) and in an independent NZ population-based series of 2625 patients in Waikato (external validation). The data included all women with primary invasive breast cancer diagnosed from 1 June 2000 to 30 June 2014, with follow up to death or Dec 31, 2014. We used multivariate Cox proportional hazards regression to assess predictors and to calculate predicted 10-year breast cancer mortality, and therefore survival, probability for each patient. We assessed observed survival by the Kaplan Meier method. We assessed discrimination by the C statistic, and calibration by comparing predicted and observed survival rates for patients in 10 groups ordered by predicted 10-year survival. We compared this NZ model with the Nottingham Prognostic Index (NPI) in this validation data set.ResultsDiscrimination was good: C statistics were 0.84 for internal validity and 0.83 for an independent external validity. For calibration, for both internal and external validity the predicted 10-year survival probabilities in all groups of patients, ordered by predicted survival, were within the 95% confidence intervals (CI) of the observed Kaplan-Meier survival probabilities. The NZ model showed good discrimination even within the prognostic groups defined by the NPI.ConclusionsThese results for the New Zealand model show good internal and external validity, transportability, and potential clinical value of the model, and its clear superiority over the NPI. Further research is needed to assess other potential predictors, to assess the model’s performance in specific subgroups of patients, and to compare it to other models, which have been developed in other countries and have not yet been tested in NZ.

Laminin 332 expression and prognosis in breast cancer

The purpose of this study was to determine the distribution of and potential significance of laminin 332 (LM332) in breast cancer. Specimens from a population-based cohort (N = 297) from 1994 to 1995 were stained for estrogen receptor (ER), progesterone receptor (PgR), HER2 and the LM332 β3 chain. Seventy-five tumors were LM332-positive and 222 were negative. LM332 β3 stained 16.0% of ER and/or PgR-positive tumors and 73.2% of triple-negative breast cancers (TNBC). Immunoblotting revealed LM332 in TNBC and HER2-positive samples, but not in an ER-positive breast carcinoma or a phyllodes tumor. After 20 years, 172 patients were alive, 43 had died of breast cancer and 82 of other causes. Patients with LM332-positive tumors had significantly worse 5 (P < .0001) and 10-year (P < .05) overall and breast cancer specific survival. Among patients with LM332 β3-expressing and ER/PgR-negative carcinomas, 10-year survival was significantly reduced (P < .0450). In a multivariate analysis LM332-positive patients had significant hazard ratios of 3.9 with 95% confidence intervals (CI) of 2.0-7.7 and 2.2 with 95% CI of 1.3-3.8 for 5 and 10-year overall survival, respectively. Because tumor cell motility is required for metastasis, the effect of LM332 on MDA-MB-231 migration was determined using siRNA. Knockdown of LM332-specific β3 and γ2 chains reduced motility without affecting viability. Our observation that LM332 in breast carcinoma is associated with decreased survival provides evidence that LM332 may have a role in the aggressive phenotype of some breast cancers.

A national multicenter study on 1072 DCIS patients treated with breast-conserving surgery and whole breast radiotherapy (COBCG-01 study)

Background and purposeBreast-conserving surgery (BCS) and whole breast radiation (RT) with or without endocrine therapy (ET) represent the standard of care for ductal carcinoma in situ (DCIS). The use of adjuvant treatments after surgery is still controversial in this setting. We performed a retrospective multicenter analysis on a series of DCIS patients treated with BCS and adjuvant RT. Materials and methodsWe collected clinical data from nine Italian centers on 1072 women having a diagnosis of DCIS and treated between 1997 and 2012. We reported on the 5- and 10-year local recurrence (LR) rates, overall survival, and breast cancer specific survival (BCSS) employing the Kaplan–Meier method. ResultsAt a median follow-up of 8.4 years, 67 LR (6.3%) and 47 deaths (4.4%) were observed. LR rates at 5 and 10 years were 3.4% and 7.6%, respectively. BCSS rates at 5 and 10 years were 99.7% and 99.1%, respectively. At univariate regression analysis, postmenopausal state (p = 0.009), estrogen receptor (ER) (p = 0.0001) and progesterone receptor (p = 0.018) positivity and ET (p = 0.006) were inversely correlated with LR. Final surgical margins (FSM) status <1 mm was significantly correlated with higher LR (p = 0.003). At multivariate regression analysis postmenopausal state (p = 0.03), and ER positive (p = 0.045) maintained the significant favorable feature, while FSM <1 mm (p = 0.024) confirmed its negative impact on LR. ConclusionsOur real-life study pointed out the significant favorable prognostic role of postmenopausal state and ER positive status on LR occurrence. FSM <1 mm was significantly correlated to a higher chance to experience LR.

Tubular carcinomas of the breast: an epidemiologic study.

We explored the clinicopathologic characteristics, prognostic factors and outcomes in tubular carcinoma (TC) of the breast. We retrospectively assessed 8091 TC patients using the SEER database from 2000 to 2013. Most patients were non-Hispanic white, well-differentiated disease, tumor size ≤2cm, node-negative, nonmetastatic, hormone receptor-positive and HER2-negative status. The 10-year breast cancer-specific survival and overall survival were 98.1 and 82.0%, respectively. Multivariate analysis indicated that age, ethnicity, surgery procedures, radiotherapy and chemotherapy were independent predictors affecting survival outcomes. There was comparable breast cancer-specific survival between surgery and nonsurgery groups. The patients with TC has excellent survival outcomes, which may in part be due to the favorable tumor characteristics.

Survival following breast-conserving therapy is equal to that following mastectomy in young women with early-stage invasive lobular carcinoma

BackgroundPrevious observational studies reported the superior survival of patients with early-stage breast cancer who underwent breast-conserving therapy (BCT, lumpectomy plus postsurgical radiation) compared to that of those who underwent mastectomy. Invasive lobular carcinoma (ILC) is not the same disease as invasive ductal carcinoma (IDC) as it has distinct biologic features and thus requires unique consideration and research. MethodsWe selected women (≤50 years of age) from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with stage T1–2, N0–1, M0 primary breast cancer with invasive lobular features between 1998 and 2011, that were treated with either BCT or mastectomy with and without radiation. We assessed survival proportions using the Kaplan-Meier method and hazard ratios using Cox proportional hazards models. Breast cancer-specific survival (BCSS) served as the primary endpoint. ResultsA total of 3393 eligible young ILC patients were identified, 1391 (41%) of which underwent lumpectomy followed by radiation. The 10-year BCSS rates for patients who received BCT, mastectomy alone and mastectomy with radiation were 95.7%, 94.2% and 89.3%, respectively. Multivariate analysis showed that BCSS was not improved in patients assigned to mastectomy alone group (HR = 0.86; 95% CI 0.57–1.28) or mastectomy with postsurgical radiation group (HR = 0.97; 95% CI 0.58–1.62) compared to that in those who underwent BCT. The results did not changed when evaluating the 1998–2004 and 2005–2011 time periods separately. ConclusionNone of the treatment demonstrated an absolute superiority in young women with early-stage ILC. Future studies with more detailed analyses of the confounding factors are worthwhile.

Abstract 2971: Digital image analysis based IHC4+C assay and prognosis in hormone receptor-positive breast cancer

Abstract Background The immunohistochemical (IHC) 4 + clinical treatment score (C) i.e. IHC4+C assay combines IHC assessment of four routinely measured markers in the clinical setting, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and KI67, with other clinical parameters for aiding decision-making on adjuvant chemotherapy in hormone positive (HR+) breast cancer. It is low cost, widely available and has been shown to provide similar prognostic information to the 21-gene (Oncotype DX) test. Clinical use of IHC4+C is limited by the need for standardized scoring of the IHC markers. Here, we examine the prognostic value of a digital image analysis (DIA) based IHC4+C assay in two study populations and compare this with pathologists' visual assay in a subset of patients. We also evaluated its potential clinical relevance in relation to the Nottingham prognostic index [NPI; i.e. low (&amp;lt;3.4), intermediate (3.4-5.4) and high (&amp;gt;5.4)] and IHC defined breast cancer subtypes (i.e. luminal A-like and B-like). Methods Using DIA data on ER, PR, HER2 and KI67, in addition to clinicopathological characteristics of tumors, we computed DIA based IHC4+C (i.e. DIAIHC4+C) assay for 2,034 women from study populations in Poland (PBCS) and the United Kingdom (SEARCH). A total of 246 deaths occurred over a median follow-up period of 6.7 years. A relevant threshold was determined using quartile analysis and the relationship between dichotomous categories (&amp;gt;75th vs ≤ 75th percentile) of DIAIHC4+C and 10-year breast cancer specific survival (BCSS) was investigated using Kaplan-Meier survival curves and in Cox proportional hazard regression models, overall and stratified by study, NPI and subtype. Results DIAIHC4+C score was associated with worse 10-year BCSS overall [HR (95% CI) &amp;gt;75th vs ≤ 75th percentile = 2.92 (1.77, 4.82); p-value &amp;lt;0.0001] and in both the PBCS [3.48 (1.40, 8.65); p-value = 0.007] and SEARCH [3.87 (2.24, 6.68); p-value &amp;lt;0.0001] study populations. DIAIHC4+C was associated with significantly worse survival outcomes in women with intermediate NPI [1.94 (1.31, 2.88); p-value = 0.001] and luminal A-like subtype of HR+ tumors [5.37 (3.50, 8.26); p-value &amp;lt;0.0001]. DIA and visual IHC4+C results were highly correlated (r = 0.95) and survival associations and model fit parameters were similar for DIA [3.82 (2.08, 7.00); p-value &amp;lt; 0.0001; AIC = 472.3] and visual [4.73 (2.55, 8.76); p-value &amp;lt; 0.0001; AIC = 466.1] IHC4+C scores amongst 444 patients with data from both sources. Conclusion These findings are in support of the prognostic value of DIAIHC4+C assay in HR+ breast cancer and demonstrate its potential clinical relevance as an adjunct to the NPI. Given the advantages of being high-throughput and highly reproducible, DIA based methods could find use in the standardization of the analytical processes for the IHC4+C assay. Citation Format: Mustapha Abubakar, Paul D. Pharoah, Mark E. Sherman, Montserrat Garcia-Closas, Mitch Dowsett. Digital image analysis based IHC4+C assay and prognosis in hormone receptor-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2971.

Omission of Postoperative Radiotherapy in Women Aged 65 Years or Older With Tubular Carcinoma of the Breast After Breast-Conserving Surgery.

To investigate the temporal trends of postoperative radiotherapy (RT) administration and the effects of omitting postoperative RT on breast cancer-specific survival (BCSS) in women aged ≥65 years with tubular carcinoma (TC) of the breast who received breast-conserving surgery (BCS). We included women aged ≥65 years with non-metastatic TC of the breast who underwent BCS between 2000 and 2013 using the Surveillance, Epidemiology, and End Results database. Statistical analyses were performed using chi-square tests, Kaplan-Meier analyses, Cox proportional hazards models, and a 1:1 propensity score matching (PSM). Before PSM, a total of 1,475 patients with tumor size ≤2 cm, node-negative disease, and estrogen receptor-positive disease were identified, including 927 (62.8%) underwent postoperative RT and 548 (37.2%) had postoperative omission of RT. The administration of postoperative RT steadily declined over the study period. Patients with younger age, larger tumor size, and other race/ethnicity were more likely to receive postoperative RT. The median follow-up duration was 85.0 months, the 5- and 10-year BCSS rates were 98.7 and 97.9%, respectively. The median BCSS was 161.9 and 165.0 months for patients with and without postoperative RT, respectively, and the corresponding 5-year BCSS rates were 98.5 and 98.8%, respectively (p = 0.134). Prognostic analysis indicated that postoperative RT was not associated with improved BCSS rates compared with RT omission (p = 0.134). After PSM, a total of 431 complete pairs were generated. In the matched population, the 5-year BCSS rates were 98.6 and 98.4% in non-postoperative RT and postoperative RT groups, respectively (p = 0.858). The univariate analyses also confirmed that the administration of postoperative RT was not associated with better BCSS (p = 0.858). The incidence of breast cancer-related death is probably sufficiently low to avoid postoperative RT in women aged ≥65 years with TC of the breast after BCS.