Lower Breast Cancer-specific Survival Research Articles

Abstract 5405: Expression of cathepsin D in early-stage breast cancer and its prognostic and predictive value

Abstract Purpose: Cathepsin D is a proteolytic enzyme that is normally localized in the lysosomes and is involved in the malignant progression of breast cancer. The expression of Cathepsin D is regulated by steroid hormones including oestrogen and growth factors. There are conflicting results between different studies regarding Cathepsin D significance as prognostic and predictor marker in breast cancer. Furthermore, Cathepsin D has not been recommended for clinical use by the American Society of Clinical Oncology because of insufficient evidence. This study was aimed to fill the gap in the lack of recent and large studies on prognostic significance of Cathepsin D expression by studying a large well-characterized series of primary breast cancer for cathepsin D expression using immunohistochemistry. Methods: Expression of Cathepsin D was assessed by immunohistochemical staining of tissue microarrays, in a large well-characterized series of early-stage operable breast cancer (n=954) from Nottingham Primary Breast Carcinoma Series between the period of 1988 and 1998 who underwent primary surgery. Correlation of cathepsin D expression with clinicopathological parameters and prognosis was evaluated. Results: Cathepsin D expression was positive in 28.8% (275/954) of breast cancer tumors. Positive expression of cathepsin D was significantly associated with high histological grade (p=0.007), pleomorphism (p=0.002), poor Nottingham Prognostic Index score (NPI) (p<0.002), recurrence (p=0.005) and distant metastasis (p<0.0001). Kaplan-Meier analysis showed that Cathepsin D expression was significantly associated with shorter breast cancer specific survival (BCSS) (p=0.001), higher risk of recurrence (p=0.001) and distant metastasis (p<0.0001). Cathepsin D positive tumors with ER positive staining who were treated with tamoxifen were associated with lower BCSS and higher risk of developing distant metastasis (p=0.001). Conclusion: This study shows Cathepsin D expression as a promising prognostic biomarker for early operable invasive breast cancer. Our results indicate that Cathepsin D expressing tumors are associated with shorter breast cancer specific survival and higher risk of recurrence and metastasis. Cathepsin D could be clinically useful to predict response to tamoxifen treatment. Targeting Cathepsin D either through inhibition of action or interference with the proteolytic pathway could be used to treat metastatic breast cancers expressing Cathepsin D. Citation Format: Inas M. Alhudiri, Christopher C. Nolan, Ian O. Ellis, Emad A. Rakha, Adam Elzagheid, Andrew R. Green, Caroline J. Chapman. Expression of cathepsin D in early-stage breast cancer and its prognostic and predictive value [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5405.

Structural Racism and Breast Cancer-specific Survival: Impact of Economic and Racial Residential Segregation.

To analyze the effect of economic and racial/ethnic residential segregation on breast cancer-specific survival (BCSS) in South Florida, a diverse metropolitan area that mirrors the projected demographics of many United States regions. Despite advances in diagnosis and treatment, racial and economic disparities in BCSS. This study evaluates these disparities through the lens of racial and economic residential segregation, which approximate the impact of structural racism. Retrospective cohort study of stage I to IV breast cancer patients treated at our institution from 2005 to 2017. Our exposures include index of concentration at the extremes, a measurement of economic and racial neighborhood segregation, which was computed at the census-tract level using American Community Survey data. The primary outcome was BCSS. Random effects frailty models predicted that patients living in low-income neighborhoods had higher mortality compared to those living in high-income neighborhoods [hazard ratios (HR): 1.56, 95% confidence interval (CI): 1.23-2.00]. Patients living in low-income non-Hispanic Black and Hispanic neighborhoods had higher mortality compared to those living in high-income non-Hispanic White (NHW) neighborhoods (HR: 2.43, 95%CI: 1.72, 3.43) and (HR: 1.99, 95%CI: 1.39, 2.84), after controlling for patient characteristics, respectively. In adjusted race-stratified analysis, NHWs living in low-income non-Hispanic Black neighborhoods had higher mortality compared to NHWs living in high-income NHW neighborhoods (HR: 4.09, 95%CI: 2.34-7.06). Extreme racial/ethnic and economic segregation were associated with lower BCSS. We add novel insight regarding NHW and Hispanics to a growing body of literature that demonstrate how the ecological effects of structural racism-expressed through poverty and residential segregation-shape cancer survival.

Prognostic Analysis of Primary Breast Signet Ring Cell Carcinoma and Mucinous Breast Adenocarcinoma: A SEER Population-Based Study.

BackgroundPrimary breast signet ring cell carcinoma (SRCC) is a rare type of breast cancer with typical morphological characteristics, high aggressiveness, and poor prognosis. SRCC is different from mucinous breast adenocarcinoma (MBC). However, only a few studies have explored the clinicopathological features and prognosis of SRCC and MBC.MethodsData retrieved from the Surveillance, Epidemiology, and End-Results (SEER) database (2004–2015) were used to explore the prognostic effect of clinicopathological features and treatment modalities on survival outcomes of SRCC and MBC patients. Kaplan–Meier plot analysis, multivariate Cox proportional risk model, propensity score matching (PSM), and subgroup analysis were performed.ResultsA total of 167 patients with SRCC and 11,648 patients with MBC were included in the study. SRCC patients exhibited higher histological grade (p < 0.001), larger tumor volume (p < 0.001), higher rate of lymph node metastasis (p < 0.001), and higher frequency of distal metastasis (p < 0.001) compared with MBC patients. Cox proportional hazards regression analysis showed that SRCC patients had lower overall survival (OS) and breast cancer-specific survival (BCSS) compared with MBC patients. Subgroup survival analysis showed that the SRCC patients had lower OS and BCSS in subgroups including younger than 60 years old, white race, married, without chemotherapy, and received radiotherapy compared with the MBC patients in these subgroups. In addition, the SRCC patients had lower BCSS in subgroups including other races (including Asian or Pacific Islander and American Indian/Alaska Native), without surgery, and lymph node metastasis.ConclusionThe findings showed that primary breast SRCC patients have unique clinical characteristics and worse prognosis compared with MBC patients. Notably, different treatment methods resulted in different prognosis for SRCC and MBC types; therefore, SRCC patients should be distinguished from MBC patients to improve efficacy of treatment.

Systemic therapy and prognosis of older patients with stage II/III breast cancer: A large-scale analysis of the Japanese Breast Cancer Registry

AimThis study aimed at investigating the real-world prognostic impact of systemic treatment in older patients with stage II/III breast cancer (BC). MethodsThis retrospective cohort study included patients with stage II/III primary BC, aged ≥55 years, and registered in the Japanese Breast Cancer Registry from 2004 to 2011. The clinicopathological characteristics, treatments, and prognosis of patients aged ≥75 years (older) were compared to those of younger patients. ResultsIn total, 56,093 patients (12,727, ≥75 years; 17,860, 65–74 years; 25,506, 55–64 years) were enrolled. In the older group, 9.2% with a luminal (hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]-), 32.9% with a triple-negative (TN, HR-/HER2-), and 27.4% with a HER2-positive (any-HR/HER2+) receptor were administered chemotherapy. In those with luminal cancer, the 5-year breast cancer-specific survival (BCSS) was approximately 95% in all age groups. Meanwhile, among those with TN and HER2-positive BC, the older group had a poorer BCSS. The 5-year overall survival (OS) was also poorer in the older group across all subtypes. Among older patients matched using clinicopathological factors, chemotherapy use was associated with improved OS in the luminal and HER2-positive subtypes. ConclusionsChemotherapy use was lower among older patients with stage II/III breast cancer. Those with TN and HER2-positive BC had a lower BCSS than their younger counterparts. Chemotherapy may be beneficial in improving the OS in older patients with luminal and HER2-positive BCs. Treatment for older patients should be individualized, based on tumor-related factors, quality of life, and the patient’s health status.

Sentinel Node Biopsy Should Not be Routine in Older Patients with ER-Positive HER2-Negative Breast Cancer Who Are Willing and Able to Take Hormone Therapy.

The SSO Choosing Wisely campaign recommended selective sentinel lymph node biopsy (SLNB) in clinically node-negative women aged ≥ 70 years with ER+ breast cancer. We sought to assess the association of SLNB positivity, adjuvant treatment, and survival in a population-based cohort. Women aged ≥ 70 years treated for ER+ HER2- breast cancer between 2010 and 2016 were identified in our prospective provincial database. Overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Kaplan-Meier analysis. Multivariable logistic regression was used to assess the association of SLNB positivity with use of adjuvant treatments and survival outcomes. We identified 2662 patients who met study criteria. SLNB was positive in 25%. Increased use of chemotherapy (ChT), hormone therapy (HT), and radiotherapy (RT) was significantly associated with SLNB positivity. Five-year OS was 86%, and BCSS was 96% with median follow-up of 4.3 years. BCSS was worse with grade 3 disease (HR 4.1, 95% CI 2.1-8.1, p < 0.0001) and better with HT (HR 0.5 95% CI 0.3-0.9, p = 0.01). Patients with a positive SLNB treated without adjuvant therapy had lower BCSS (HR 3.2 95% CI 1.2-8.4, p = 0.017) than those with a negative SLNB, but patients with a positive SLNB treated with any combination of ChT, HT, and/or RT, had similar BCSS to those with a negative SLNB. BCSS in this population was excellent at 96%, and BCSS was similar with negative and positive SLNB when patients received HT. SLNB can be omitted in elderly patients willing to take HT.

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

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

The longitudinal risk of mortality between invasive ductal carcinoma and metaplastic breast carcinoma

The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.

Incorporation of biologic factors for the staging of de novo stage IV breast cancer

This study aimed to investigate the prognostic value of biological factors, including histological grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status in de novo stage IV breast cancer. Based on eligibility, patient data deposited between 2010 and 2014 were collected from the surveillance, epidemiology, and end results database. The receiver operating characteristics curve, Kaplan–Meier analysis, and Cox proportional hazard analysis were used for analysis. We included 8725 patients with a median 3-year breast cancer-specific survival (BCSS) of 52.6%. Higher histologic grade, HER2-negative, ER-negative, and PR-negative disease were significantly associated with lower BCSS in the multivariate prognostic analysis. A risk score staging system separated patients into four risk groups. The risk score was assigned according to a point system: 1 point for grade 3, 1 point if hormone receptor-negative, and 1 point if HER2-negative. The 3-year BCSS was 76.3%, 64.5%, 48.5%, and 23.7% in patients with 0, 1, 2, and 3 points, respectively, with a median BCSS of 72, 52, 35, and 16 months, respectively (P < 0.001). The multivariate prognostic analysis showed that the risk score staging system was an independent prognostic factor associated with BCSS. Patients with a higher risk score had a lower BCSS. Sensitivity analyses replicated similar findings after stratification according to tumor stage, nodal stage, the sites of distant metastasis, and the number of distant metastasis. In conclusion, our risk score staging system shows promise for the prognostic stratification of de novo stage IV breast cancer.

Expression of H3K4me3 and H3K9ac in breast cancer

PurposeBreast cancer is the leading cause of cancer death in females. Histone modifications have been shown to have an influence on the gene expression. This study focusses on the histone modifications H3K9ac and H3K4me3 in breast cancer and their impact on survivalMethodsH3K4me3 and H3K9ac expression was immunohistochemically examined in 235 tissue samples.ResultsPositive estrogen receptor status was correlated with a higher IRS of the nuclear (p = 0.033), and of the cytoplasmic H3K4me3 staining (p = 0.009). H3K9ac intensity was associated to the Her2 status (p = 0.045) and to poor prognosis in cells with positive Ki67 status (p = 0.013). A high intensity of nuclear H3K4me3 staining was found to be correlated with a lower 10-year-survival (p = 0.026) and with lower breast cancer-specific survival (p = 0.004). High percentage score (> 190) of H3K9ac expression was correlated to worse breast cancer-specific survival (p = 0.005). Shorter progression-free survival was found in patients with nuclear (p = 0.013) and cytoplasmic H3K4me3expression (p = 0.024) and H3K9ac expression (p = 0.023).ConclusionThis analysis provides new evidence of histone modifications in breast cancer. High H3K4me3 and H3K9ac expression was correlated with survival rates. Further investigation of histone modifications in breast cancer could lead to a more profound understanding of the molecular mechanisms of cancer development and could result in new therapeutic strategies.

Abstract P2-08-03: Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence and an increased risk of breast cancer mortality in women with ductal carcinoma in situ treated with breast-conserving therapy

Abstract Purpose: Ductal Carcinoma in Situ (DCIS) with microinvasion (MI) (&amp;lt; 1mm) includes a spectrum of cases with a single focus of MI and those with multiple foci (2 or more) of MI. The impact of multiple foci of MI on the risks of local recurrence (LR), invasive LR and breast cancer-specific survival (BCSS) is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment than those with a single focus of MI or pure DCIS. We examined the impact of multiple foci of MI, confirmed by expert pathology review, on the 15-yr risks of LR, invasive LR and breast-cancer specific survival (BCSS) in a population cohort of DCIS (+/-MI) treated with breast-conserving surgery (BCS) +/- radiotherapy (RT). Methods: The cohort includes all women diagnosed with DCIS +/- MI in Ontario from 1994-2003 treated with BCS+/-RT. Cases with prior malignancy were excluded. Treatment and outcomes were ascertained by deterministic linkage with chart validation. Cause of death was determined from the provincial cancer registry or terminal hospital admission records. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of ipsilateral invasive LR and ipsilateral DCIS LR, adjusting for significant co-variates. The 15-yr invasive local recurrence-free survival (LRFS), DCIS LRFS and 15-yr BCSS risks were calculated using the Kaplan-Meier method with differences compared using the log-rank test. Results: The cohort includes 3529 women; 2988 (85%) with pathology review are included in this analysis. 2,721 had pure DCIS (51% received RT), 267 had DCIS with MI (1 focus, N=156; multiple foci, N=111 (58% had RT)). Median follow-up was 13 years. Median age at diagnosis was 58 years. LR developed in 571 cases (21%) of pure DCIS, 33 cases (21%) with 1 focus of MI and 23 cases (27%) with multiple foci of MI. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR=1.59, 95%CI: 1.01-2.49, p=0.04) but not DCIS LR (HR=0.89, 95%CI: 0.46, 1.76, p=0.7). Women with multiple foci of MI had higher risks of invasive LR and lower BCSS at 15 years compared to those with pure DCIS. The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% for cases treated by BCS alone and 87.2%, 89.9% and 77% following BCS+RT without boost; however, women treated with boost RT had substantially higher 15-yr invasive LRFS risks than those who did not receive boost RT. The 15-yr invasive LRFS risks for those with pure DCIS, 1 or multiple foci of MI, were 89.2%, 91.3% and 95% (all p values&amp;gt;.05, limited by low event rate). The 15-yr BCSS risks for cases with 1 focus, multiple foci of MI or pure DCIS were 92.1%, 93.1%, 96.4% (p=.006). Conclusions: The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR and lower breast-cancer specific survival after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk. Citation Format: Rakovitch E, Sutradhar R, Lalani N, Gu S, Nofech-Mozes S, Hanna W, Fong C, Paszat L. Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence and an increased risk of breast cancer mortality in women with ductal carcinoma in situ treated with breast-conserving therapy [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 P2-08-03.

Effect of lymph node metastasis size on breast cancer-specific and overall survival in women with node-positive breast cancer.

We investigated whether increasing size of lymph nodes (LN) metastases is associated with lower breast cancer-specific survival (BCSS) and overall survival (OS) independent of the number of positive LNs. Using Surveillance, Epidemiology, and End Results registry data, we identified 8791 women diagnosed between 1990 and 2003 with node-positive, non-metastatic invasive breast cancer treated with surgery and axillary LN dissection. Size of the largest involved LN metastasis was categorized as ≤2 mm, >2 mm to <2 cm, and ≥2 cm. BCSS and OS were estimated using the Kaplan-Meier method and compared using log-rank statistics. Adjusted hazard ratios (HR) were calculated using Cox proportional hazards models. Median follow-up was 109 months. Largest LN size was ≤2 mm, >2 mm to <2 cm, and ≥2 cm in 2219 (25.2 %), 5047 (57.4 %), and 1525 (17.3 %) women, respectively. The 10-year BCSS for women with LNs ≤2 mm, >2 mm to <2 cm, and ≥2 cm was 82.9, 75.5, 64.8 %, respectively (p < 0.001). On multivariable analysis, large (≥2 cm) LN size was significantly associated with worsened BCSS (HR: 1.169; p = 0.026) and OS (HR: 1.169; p = 0.006) in addition to age, race, grade, PR status, adjuvant radiation, T-stage, and number of positive LNs. Large (≥2 cm) LNs metastases were associated with lower BCSS and OS after controlling for other known prognostic factors including number of positive LNs. LN size could be useful to risk-stratify patients for adjuvant therapy if these results are validated in future prospective studies.

Socioeconomic and racial disparities in the selection and outcomes of a chest-wall boost in post-mastectomy radiation therapy.

14 Background: We investigated socioeconomic and racial disparities in the selection and outcomes of patients from the California Cancer Registry receiving post-mastectomy radiation therapy (PMRT) with or without a chest-wall boost (CWB). Methods: Records of 5,586 women with invasive breast cancer, diagnosed from 2005-2009, treated with PMRT were reviewed and stratified based on treatment with (n=2,482 [44%]) or without (n=3,104 [56%]) a CWB. Race and socioeconomic status (SES) between the cohorts were analyzed. Bivariate analyses of the impact of race and socio-demographic factors on breast cancer-specific survival (BCS) and overall survival (OS) were performed using the Kaplan-Meier method. Adjusting for potential confounders, we used multivariate proportional hazards models to identify predictors of BCS and OS, reported as hazard ratios (HR) with 95% confidence intervals (CI). Results: The majority of PMRT patients were white (58%), compared to Hispanic (20%), Asian/Pacific-Islander (15%), and black (6%). Most were of high SES (50%), compared to middle (21%) or low (29%). Non-white patients were more frequently of low SES (59% vs. 40%). Hispanic frequency (61%) of advanced-stage (3-4) disease was the highest of all races. Low SES was also associated with higher stage (37% vs. 60%) compared to high SES, which comparatively presented with lower-stage (1-2) disease (42% vs. 57%, p=0.0187). Low-SES patients were more likely to receive a CWB (31 vs. 26%) while high-SES patients were less likely (48% vs. 53%, p&lt;0.0001). White women were more likely to be treated without a CWB (60 vs. 57%), while Hispanic women were less likely (23% vs. 18%, p=0.0003). Women not treated with a CWB with low SES had a lower BCS (HR 1.541 p=0.0114) and OS (HR 1.794. p=&lt;0.001) compared to women of high SES. Black women not treated a CWB had lower OS (HR 1.712, p=0.0249) compared to similarly-treated white women. Conclusions: Low SES and Hispanic race were associated with advanced stage, and more commonly treated with a CWB. Low-SES and black women treated without a CWB had lower OS, while the former also had lower BCS. These findings suggest that economic and racial health-care disparities contribute to worse outcomes.

Patients younger than 40years old and older than 70years old affected by ER(−)/PR(−)/HER2(−) breast cancer have low survival rates: Results of a mono-institutional retrospective analysis

Abstract Objective The aim of this study is to evaluate the survival and tumor characteristics, including breast cancer phenotypes, of older patients affected by breast cancer and compare these results with those of younger patients. Materials and Methods Data of 890 patients were analyzed. Patient characteristics and outcomes were evaluated among women aged ≤ 40 vs 41–50 vs 51–60 vs 61–70 vs > 70 years old. Results Patients > 70 years old had more frequently a HER2(+) breast cancer phenotype and positive axillary nodes and had lower breast cancer specific survival and distant metastases free survival rates. When analysed for ER(−)/PR(−)/HER2(−) phenotype, younger and older patients had lower survival compared with other age subgroups. Conclusions In our study, patients younger than 40 years old and older than 70 years affected by ER(−)/PR(−)/HER2(−) breast cancer have lower survival. Considering that there is no common behavior on how to treat older patients affected by this particular breast cancer phenotype, there is an increasing need to enroll older patients in clinical trials in order to realize tailored standards of care.

The Impact of Diabetes Mellitus on Prognosis of Early Breast Cancer in Asia

Diabetes mellitus (DM) has been implicated in influencing the survival duration of patients with breast cancer. However, less is known about the impact of DM and other comorbidities on the breast cancer-specific survival (BCS) and overall survival (OS) outcomes of Asian patients with early-stage breast cancer. The characteristics of female patients with newly diagnosed, early-stage breast cancer were collected from the Taiwan Cancer Registry database for 2003-2004. DM status and other comorbidities were retrieved from Taiwan's National Health Insurance database. The BCS and OS times of patients according to DM status were estimated via the Kaplan-Meier method. Cox's proportional hazard model was used to estimate adjusted hazard ratios (HRs) for the effects of DM, comorbidities, and other risk factors on mortality. In total, 4,390 patients were identified and 341 (7.7%) presented with DM. The 5-year BCS and OS rates were significantly greater in DM patients than in non-DM patients (BCS, 85% versus 91%; OS, 79% versus 90%). Furthermore, after adjusting for clinicopathologic variables and comorbidities, DM remained an independent predictor of shorter BCS (adjusted HR, 1.53) and OS (adjusted HR, 1.71) times. Subgroup analyses also demonstrated a consistent prognostic influence of DM across different groups. In Asian patients with early-stage breast cancer, DM is an independent predictor of lower BCS and OS rates, even after adjusting for other comorbidities. The integration of DM care as part of the continuum of care for early-stage breast cancer should be emphasized.

Defining breast cancer prognosis based on molecular phenotypes: results from a large cohort study.

Abstract Abstract #1068 Aim&amp;#x2028; Identification at the molecular level of breast cancers sub-types associated with different clinical outcomes would be of great value to help individualize therapeutic strategies and, in turn, improve survival. With large sample size, long follow-up, and geographical spread of the population any results derived from analysis of the Nurses' Health Study (NHS) data set may be more generalizable to the U.S population. Thus the purpose of this study was to define the survival outcomes associated with distinct molecular phenotypes of invasive breast cancer in women identified from the NHS.&amp;#x2028; Methods&amp;#x2028; 2013 women enrolled in the NHS (1976-1996) with invasive non-metastatic breast cancer whose breast tumor samples were available for inclusion in tissue microarrays and subsequent immunohistochemical (IHC) analysis form the study population. Tumors were classified into one of 5 categories based on results of IHC assays for estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin (CK) 5/6, and epidermal growth factor receptor (EGFR) as follows: 1) Luminal-A (ER and/or PR +ve and HER2 -ve), 2) Luminal-B (ER and/or PR +ve and HER2 +ve), 3) HER2 subtype (HER2 +ve with both ER and PR -ve), 4) Basal-like (-ve for ER, PR and HER2 and +ve for either CK5/6 and/or EGFR), 5) unclassifiable (-ve for all markers). Overall survival (OS), breast-cancer-specific survival (BCS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meir product limit method and compared across groups using the log rank statistic. Cox-proportional hazards models were fitted to determine the association of molecular phenotype with survival outcomes after adjusting for age at diagnosis, stage, lymph nodes, tumor size, grade and body mass index at diagnosis.&amp;#x2028; Results&amp;#x2028; Median age at diagnosis was 57 years (34 – 75 years) with a median follow-up of 14 years. 1490 (74%) tumors were classified as luminal-A, 99 (4.9%) were classified as luminal-B, 106 (5.27%) were of HER2 subtype, 219 (10.9%) were classified as basal-like and 99 (4.9%) tumors were unclassifiable.726 (36%) patients had died of any cause, 433 (21.5%) had died of a breast cancer related event, and 459 (22.8%) experienced a recurrence. Five-year BCS for patients with luminal-A, luminal-B, HER2 , basal-like and unclassifiable tumors was 94%, 82%, 73%, 82% and 75% respectively (p&amp;lt;0.001). In the fully adjusted multivariable model compared to patients with luminal-A tumors patients with luminal-B (HR 1.73, 95% 1.18-2.53), HER2 (HR 1.39, 95% CI 0.97-1.20), basal-like (HR 1.50, 95% 1.32-1.20) and unclassifiable (HR 1.89, 95% CI 1.30-2.74) tumors had lower BCS. Similar trends were observed for OS and RFS.&amp;#x2028; Conclusions&amp;#x2028; Compared to women who have luminal-A tumors those with luminal-B, HER2 subtype, basal-like and unclassifiable tumors had a worse prognosis. A fifth, unclassifiable sub-group was identified that has survival outcomes similar to and may represent a subtype of basal-like tumors. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1068.

Age-related variations in the use of axillary dissection: a survival analysis of 8038 women with T1–ST2 breast cancer

Purpose : The use of axillary dissection (AD) in women with invasive breast cancer is increasingly questioned. This study analyzes the survival in women with T1–2 breast cancer according to age and AD use. Methods and Materials : Data from the Breast Cancer Outcomes Unit Database were analyzed for 8038 women aged 50–89 years referred to the British Columbia Cancer Agency between 1989 and 1998 with invasive T1–2,M0 breast cancer. Tumor and treatment characteristics were compared between women treated with and without AD (AD+ vs. AD−) according to three age groups: 50–64, 65–74 and 75+ years. Regional relapse and actuarial 5-year overall and breast cancer-specific survival were compared between AD+ and AD− women. Multivariate analysis of age, tumor and treatment factors, and adjusted hazard ratios with AD omission were performed. Results : AD was omitted more frequently with advancing age (4% vs. 8% vs. 22% in women aged 50–64, 65–74, and 75+ years, respectively, p <0.0001). Tumor characteristics were more favorable in AD− women, with fewer having Grade III disease, T2 tumors, or lymphovascular invasion (all p <0.0001). Women treated without AD were also less likely to undergo radiotherapy after lumpectomy or mastectomy (both p <0.0001). Systemic therapy use and regional relapse rates were comparable between AD− and AD+ women in each age-specific cohort. Multivariate analysis identified age, tumor size, grade, lymphovascular invasion, estrogen receptor status, clinical nodal palpability, type of surgery, and radiotherapy use as independent variables affecting survival. Hazard ratios adjusted for these variables showed AD omission to be associated with lower overall survival in the entire cohort (hazard ratio 1.52, p <0.0001) and lower breast cancer-specific survival in women aged 65–74 years (hazard ratio 1.99, p = 0.02). Conclusion : AD was more frequently omitted with advancing age. The lack of differences in systemic therapy use, regional relapse, and breast cancer-specific survival among AD− compared with AD+ women aged 75+ years suggests that AD use may be selectively omitted in this elderly cohort. However, the lower survival associated with AD omission among women aged 65–74 years, and the lack of a survival advantage among AD− women aged 50–64 years despite more favorable tumor characteristics and comparable systemic therapy use support the hypothesis that definitive locoregional therapy has an impact on survival.