Evaluating the preoperative breast cancer characteristics affecting the accuracy of axillary ultrasound staging

We evaluate the preoperative breast cancer (BC) characteristics that affect the diagnostic accuracy of axillary ultrasound (US) and determine the reliability of US in the different subgroups of BC patients. Axillary US assessments in women with invasive BC diagnosed between 2009 and 2016 in a single institution were retrospectively reviewed. The diagnostic accuracy of axillary US was obtained using surgical nodal histology as the gold standard. Preoperative breast tumor sonographic and histological factors affecting axillary US diagnostic accuracy were examined. Of the 605 newly diagnosed invasive BC cases reviewed, 251 (41.5%) had nodal metastases. Axillary US sensitivity was 75.7%, specificity 92.9%, positive predictive value 88.4%, negative predictive value 84.4%, and false‐negative rate 24.3%. Lower US sensitivity was seen with invasive lobular cancer (ILC) (P = .043), grade I/II, (P = .021), unifocal (P = .039), and smaller tumors (P < .001). US specificity was lower in grade III (P < .001), estrogen receptor (ER)‐negative (P < .001), progesterone receptor (PR)‐negative (P = .004), HER2‐positive (P = .015), triple‐negative (P = .001), and larger breast tumors (P < .001). US has moderate sensitivity and good specificity in detecting metastatic axillary lymph nodes. Based on preoperative cancer characteristics, US was less sensitive for nodal metastases from ILC, unifocal, lower grade, and smaller breast tumors. It was also less specific in grade III, ER‐negative, PR‐negative, HER2‐positive, triple‐negative, and larger breast tumors. Caution is suggested in interpreting the US axillary findings of patients with these preoperative tumor features.     

The Relationship of Race,Oncotype DX,and Ki67 in a Population Highly Screened For Breast Cancer

Oncotype DX recurrence score (ODX) can predict risk of invasive breast cancer recurrence and benefit of chemotherapy. Literature is limited on the relationship of ODX and race in women with hormone receptor positive and node negative/positive disease. Our study examines the relationship between race and clinical characteristics within a population of highly screened women with newly diagnosed breast cancer. The institutional Breast Cancer Database was queried for patients with newly diagnosed breast cancer between January2010 and March2015. We analyzed clinical and tumor characteristics including ODX. Statistical analyses included Pearson's Chi‐Square and Fisher's Exact Tests. There were 2,092 women in our study cohort. The majority had college‐level education (84%), regular screening (78%), and clinical breast exams (88%). The majority had invasive ductal carcinoma (IDC) (62%), early stage (0, I, II) tumors (93%), ER+ (84%), PR+ (71%), Her2 negative (86%), and node negative disease (83%). There was a significantly higher proportion of later stage disease among African‐Americans (p = 0.001) and Asians (p = 0.006) and more triple negative breast cancers among African‐Americans (p < 0.0001). A majority of patients had a low ODX (56%). While ODX was not different among the race categories (p = 0.97), there were significant racial differences in Ki‐67 (p < 0.0001). In a population of highly screened women, differences were found between races regarding tumor histology. No statistical difference between race and ODX was noted, but there were racial differences in Ki67. Therefore we recommend that further research be focused on refining management algorithms by ethnicity.     

Prognostic Value of Breast Cancer Subtypes,Ki‐67 Proliferation Index,Age, and Pathologic Tumor Characteristics on Breast Cancer Survival in Caucasian Women

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well‐established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER‐/PR‐/HER2‐) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki‐67 proliferation index (Ki‐67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000‐late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan–Meier curve. ER/PR/HER2 status, grade, tumor‐node‐metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki‐67PI was analyzed between ER/PR/HER2 groups using the Kruskal–Wallis, Mann–Whitney U‐tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1–16 times more likely to die than patients with stages IA‐B and IIA disease, respectively (95% CI 1.17–3.81 through 9.68–28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki‐67PI between ER/PR/HER2 subtypes, p < .001, but Ki‐67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki‐67 proliferation index are not.     

Is the TNM Staging System for Breast Cancer Still Relevant in the Era of Biomarkers and Emerging Personalized Medicine for Breast Cancer – An Institution's 10‐year Experience

We have previously demonstrated that TNM status and age were significant predictors of overall survival (OS) in our study population of Caucasian patients with invasive breast carcinoma (2000–2004 study period). However, estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) biomarker expression was not predictive of OS when using the five‐group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011. The current study reassessed the relevance of tumor biomarkers (ER/PR/HER2) in our study population using a recently proposed biologic TNM (bTNM) classification system in which the inclusion of triple negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM for staging, prognosis and treatment of breast cancer patients. Seven hundred eighty‐two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to 2008 were grouped according to their TNM stage and TNP versus non‐TNP ER/PR/HER2 phenotype. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01–1.97; Stage III = HR 3.96, 95% CI 2.68–5.88; Stage IV = HR 27.25, 95% CI 16.84–44.08), and age (HR 1.05, 95% CI 1.04–1.06) were significant predictors of OS. TNP significantly worsened prognosis/survival only in higher TNM stages (Stage III = HR 3.08, 95% CI 1.88–5.04, Stage IV = HR 24.36, 95% CI 13.81–42.99), but not in lower stages (I and II). Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers primarily improve the accuracy of TNM staging in advanced stages of breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St. Gallen, TNP, etc.), characteristics of populations studied (Caucasians, minorities, etc.), and the time period chosen for a study are major factors that determine impact of biomarkers on the prognostic accuracy of TNM. We propose systematic analyses of these factors before biomarkers are fully incorporated into the TNM staging system (bTNM).     

Breast Cancer Subtypes as Defined by the Estrogen Receptor (ER), Progesterone Receptor (PR), and the Human Epidermal Growth Factor Receptor 2 (HER2) among Women with Invasive Breast Cancer in California, 1999–2004

Abstract: Breast cancer research examining either molecular profiles or biomarker subtypes has focused on the estrogen receptor negative/progesterone receptor negative/human epidermal growth factor receptor 2 negative (ER−/PR−/HER2−) and ER−/PR−/HER2+ subtypes. Less is known about the epidemiology or clinical outcome of the other subtypes. This study examines the eight combinations of ER/PR/HER2 in patients with invasive breast cancer. The 5‐year relative survival and the distribution among demographic, socioeconomic, and tumor characteristics of each of the subtypes are examined. Using the California Cancer Registry, 61,309 women with primary invasive breast cancer were classified according to ER/PR/HER2 status. Five‐year relative survival was computed for the eight subtypes. Bivariate analyses were used to assess the distribution of cases across all subtypes. Multivariate logistic regression was used to compute the adjusted odds of having one of the five subtypes with the best and worst survival. Survival varied from 96% (ER+/PR+/HER2−) to 76% (ER−/PR−/HER2+ and ER−/PR−/HER2−). The four subtypes with the poorest survival were all ER negative. Women who were younger than age 50, non‐Hispanic black or Hispanic, of the lowest SES groups, and had stage IV tumors that were undifferentiated were overrepresented in ER−/PR−/HER2+ and triple negative (ER−/PR−/HER2−) subtypes. Asian Pacific Islanders had increased odds (OR = 1.41; 95% confidence interval [CI] = 1.26–1.57) of having the ER−/PR−/HER2+ subtype. Stage III tumors (OR = 1.25; 95% CI = 1.08–1.44) and stage IV tumors (OR = 1.58; 95% CI = 1.27–1.98) had higher odds than stage I tumors of being ER−/PR−/HER2+. Stage IV tumors (OR = 0.54; 95% CI = 0.44–0.67) strongly decreased the odds of the ER−/PR−/HER2− subtype. Poorly differentiated and undifferentiated tumors were over 20 times as likely as well‐differentiated tumors of being ER−/PR−/HER2− or ER−/PR−/HER2+. There are considerable differences in survival, demographics, and tumor characteristics among the eight subtypes. We recommend reporting breast cancer as an ER/PR/HER2 subtype and precisely documenting demographic and tumor characteristics.     

Outcome Following Local‐Regional Recurrence in Women with Early‐Stage Breast Cancer: Impact of Biologic Subtype

Local‐regional recurrence (LRR) after breast‐conserving therapy (BCT) can result in distant metastasis and decreased disease‐free survival (DFS). This study examines factors associated with DFS following LRR. The initial population included 2,233 consecutive women who underwent BCT from 1998 to 2007. Biologic subtype was approximated using a combination of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. Cumulative incidence of DFS after LRR was calculated. The association of clinical, pathologic, and treatment parameters with DFS was evaluated using a Cox regression model. At a median follow‐up of 105 months, 82 patients (3.7%) had a LRR. Of these, 66 (80%) were in‐breast and 16 (20%) involved the ipsilateral lymph nodes. Twenty patients subsequently developed distant metastases. Five‐year DFS after initial recurrence was 69.6% for the overall cohort. On univariate analysis, triple‐negative disease (ER/PR/HER2 negative, TNBC) was associated with reduced DFS (HR = 3.8; 95% CI: 1.8–8.1; p < 0.001). Other factors associated with reduced DFS were larger tumor size (HR = 1.3; 95% CI: 1.03–1.6; p = 0.02), shorter interval from initial diagnosis to LRR (HR = 0.98 per month; 95% CI: 0.97–0.99; p = 0.02), and no salvage surgery (HR = 0.2; 95% CI: 0.09–0.5; p = 0.001). On multivariate analysis, TNBC remained the most significant factor associated with reduced DFS (HR = 4.8; 95% CI: 2.25–10.4; p < 0.001). Compared to women with luminal A disease, those with TNBC had significantly worse DFS (37.5% versus 88.3% at 5 years; p < 0.001). Women with TNBC who developed LRR were at high risk of subsequent recurrence. Efforts should be targeted toward both preventing initial recurrence and decreasing subsequent metastasis.     

Male breast cancer: Looking for better prognostic subgroups

PurposeMale Breast Cancer (MBC) remains a poor understood disease. Prognostic factors are not well established and specific prognostic subgroups are warranted.Patients/methodsRetrospectively revision of 111 cases treated in the same Cancer Center. Blinded-central pathological revision with immunohistochemical (IHQ) analysis for estrogen (ER), progesterone (PR) and androgen (AR) receptors, HER2, ki67 and p53 was done. Cox regression model was used for uni/multivariate survival analysis. Two classifications of Female Breast Cancer (FBC) subgroups (based in ER, PR, HER2, 2000 classification, and in ER, PR, HER2, ki67, 2013 classification) were used to achieve their prognostic value in MBC patients. Hierarchical clustering was performed to define subgroups based on the six-IHQ panel.ResultsAccording to FBC classifications, the majority of tumors were luminal: A (89.2%; 60.0%) and B (7.2%; 35.8%). Triple negative phenotype was infrequent (2.7%; 3.2%) and HER2 enriched, non-luminal, was rare (≤1% in both). In multivariate analysis the poor prognostic factors were: size >2 cm (HR:1.8; 95%CI:1.0–3.4years, p = 0.049), absence of ER (HR:4.9; 95%CI:1.7–14.3years, p = 0.004) and presence of distant metastasis (HR:5.3; 95%CI:2.2–3.1years, p < 0.001). FBC subtypes were independent prognostic factors (p = 0.009, p = 0.046), but when analyzed only luminal groups, prognosis did not differ regardless the classification used (p > 0.20). Clustering defined different subgroups, that have prognostic value in multivariate analysis (p = 0.005), with better survival in ER/PR+, AR-, HER2-and ki67/p53 low group (median: 11.5 years; 95%CI: 6.2–16.8 years) and worst in PR-group (median:4.5 years; 95%CI: 1.6–7.8 years).ConclusionFBC subtypes do not give the same prognostic information in MBC even in luminal groups. Two subgroups with distinct prognosis were identified in a common six-IHQ panel. Future studies must achieve their real prognostic value in these patients.     

Invasive Micropapillary Carcinoma of the Breast: A Clinicopathologic Study of 103 Cases of an Unusual and Highly Aggressive Variant of Breast Carcinoma

Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c‐erb‐B2 overexpression of tumors were re‐evaluated. Mann–Whitney U, chi‐squared, Kaplan–Meier, and Fisher's exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high‐grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c‐erbB‐2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c‐erb‐B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log‐rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c‐erb‐B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.     

Breast cancer in young women: Pathologic features and molecular phenotype

PurposeControversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications.MethodsWe conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected.Results5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients ≤35 years old. Triple negative and HER2 tumors were predominantly found in patients ≤35 (22.2% and 22.1%, p < 0.01). A young age ≤40 years (p < 0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60–2.63) or ≤35 years (p < 0.001; [HR]: 3.86; 95% [CL]: 2.69–5.53) impacted on the indication of chemotherapy. Age ≤35 (p < 0.001; [HR]: 2.01; 95% [CL]: 1.36–2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p < 0.006; [HR]: 0.6; 95% [CL]: 0.40–0.86) and positive hormone receptor status (p < 0.001; [HR]: 0.6; 95% [CL]: 0.54–0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients >35–40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p < 0.01).ConclusionYoung women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy.     

Independent validation of stromal uPA in ABCSG-08: Level 1b evidence for the prognostic value of uPA immunohistochemistry

PurposeTo validate the prognostic role of urokinase-type plasminogen-activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) protein expression in FFPE archived tumor samples when assessed by immunohistochemistry.Patients and methodsFresh-frozen, paraffin-embedded (FFPE) samples from 303 postmenopausal women with hormone receptor-positive, early breast cancer were investigated. The patients had received 5 years of endocrine therapy in the prospectively randomized ABCSG-8 trial. Immunohistochemistry for stromal uPA and PAI-1 protein expression was correlated with distant recurrence-free survival (DRFS) and overall survival (OS).ResultsWe detected stromal uPA in 132 of 297 tumors (44.4%) and stromal PAI-1 expression in 74 out of 299 samples (24.7%). Co-expression of uPA and PAI-1 was present in 48 of 294 (16.3%) cases. Neither uPA nor PAI-1 expression was associated with tumor size, age, nodal status, grading, or quantitative receptor status. Patients whose tumor stroma expressed uPA protein had a significantly shorter DRFS (adjusted HR for relapse: 2.78; 95% CI 1.31–5.93; p = 0.008 Cox regression analysis) than women without uPA expression. No such association was seen for PAI-1 and the uPA/PAI1 ratio. After a median follow-up of 5.6 years, women with uPA-positive tumors demonstrated significantly shorter DRFS (93.3% vs. 84.8%; p < 0.013 log-rank test), and tended to have a worse OS (83.0% vs. 77.3%; p = 0.106) compared to women with uPA negative tumors.ConclusionThis independent validation in archived tumor samples from a large prospective randomized trial confirms the clinical utility of stromal uPA evaluation by immunohistochemistry. This provides level 1b evidence for the prognostic role of stromal uPA in women with endocrine-responsive early breast cancer.     

Time to initiation of neo‐adjuvant chemotherapy for breast cancer treatment does not influence patient survival: A study of US breast cancer patients

Delays in the initiation of adjuvant chemotherapy or radiation therapy are associated with worse outcomes in patients undergoing treatment for breast cancer. However, the impact of the time to initiation of neo‐adjuvant chemotherapy (NAC) on patient outcomes has not previously been studied. The purpose of this study was to determine whether delays in NAC initiation impact patient survival. The National Cancer Database was queried for women ≥ 18 years old who underwent NAC within 6 months of being diagnosed with stage I‐III invasive breast cancer in 2010‐2011. ER+ or PR+, Her2? cancers were excluded from analysis. Multivariable Cox proportional hazard modeling was used to evaluate the relationship between time to NAC, sociodemographic, diagnosis, and treatment factors with patient survival. The median age of the 12 806 women included in this study was 52 (range 21‐90) with 62% presenting with cT2 disease and 62% with nodal involvement. Half of the women (50%) had triple negative, 30% ER/PR+Her2+ and 20% ER?PR?Her2+ cancers. The median time to starting NAC was 4 weeks (range 0‐26) for all subtypes. Time to NAC initiation was not associated with a difference in survival for triple negative or Her2+ cancers. Delays from diagnosis to starting NAC are not associated with worse survival for patients with Her2+ or triple negative breast cancer. This study demonstrates that the majority of women in the modern era start NAC in a timely fashion and delays in starting NAC within 6 months of diagnosis do not impact long‐term patient outcomes.     

Poor Hormone Receptor Expression in East African Breast Cancer: Evidence of a Biologically Different Disease?

Background  Few studies have examined breast cancer hormone receptor expression in Africans. We report on the hormone receptor profile of breast cancer in East Africans in the largest prospective study for this region. Methods  Consecutive breast cancer presentations to a hospital in Kijabe (2001–2007) were included. Demographic, clinical, and test data were collected. ER/PR and Her2 testing was based on immunohistochemistry (IHC). Results  There were 129 subjects (median 47 years), most had invasive ductal cancer and locally advanced disease and/or metastases. ER/PR testing was done in 120: 24% had ER-positive tumours, 34% were ER- and/or PR-positive, 10% were ER-negative but PR-positive tumours, and 66% were negative for ER and PR. ER/PR positivity was not associated with stage (P = 0.28) and was not related to age, parity, menopausal status, or node metastases. Increasing tumour grade was associated with PR expression (P = 0.02) with decreasing frequency of PR positive tumours as histological grade increased; there was weak evidence of an association between grade and ER expression (P = 0.06). Of cases tested, 26.5% overexpressed Her2. Conclusions  Breast cancer in Kijabe is an advanced-stage disease, comprised mainly of poorly differentiated cancers that are less likely to be hormone sensitive (across all stages of disease). ER/PR testing of all those affected by breast cancer should be supported as a global priority in cancer control. International and inter-African research collaborations are needed to allow genetic detailing of tumours in indigenous Africans to assess possible racial heterogeneity in the biology of breast cancer.     

Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma?

Oncotype Dx Breast Cancer Assay is a 21‐gene assay used in estrogen receptor (ER)‐positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER‐2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision‐making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions.     

Risk of Positive Nonsentinel Nodes in Women with 1–2 Positive Sentinel Nodes Related to Age and Molecular Subtype Approximated by Receptor Status

We examine risk of positive nonsentinel axillary nodes (NSN) and ≥4 positive nodes in patients with 1–2 positive sentinel nodes (SN) by age and tumor subtype approximated by ER, PR, and Her2 receptor status. Review of two institutional databases demonstrated 284 women undergoing breast conservation between 1997 and 2008 for T1‐2 tumors and 1 (229) or 2 (55) positive SN followed by completion dissection. The median number of SN and total axillary nodes removed were 2 (range 1–10) and 14 (range 6–37), respectively. The rate of positive NSNs (p = 0.5) or ≥4 positive nodes (p = 0.6) was not associated with age. NSN were positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p = 0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0% of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was significantly associated with having NSNs positive (55% versus 24%, p < 0.0001) and with having total ≥4 nodes positive (33% versus 7%, p < 0.0001). In a population that was largely eligible for ACOSOG Z0011, the risk of positive NSN or ≥4 positive nodes did not vary significantly by age. The TN subgroup had the lowest risk of both positive NSN or ≥4 positive nodes. Several high risk groups with >15% risk for having ≥4 positive nodes were identified. Further data is needed to confirm that ACOSOG Z0011 results are equally applicable to all molecular phenotypes.     

The effect of family history on screening procedures and prognosis in breast cancer patients - Results of a large population-based case-control study

BackgroundThe potential benefit of additional breast cancer screening examinations in moderate risk patients (patients with a history of breast cancer in one or two family members) remains unclear.MethodsA large population-based case–control study on breast cancer in postmenopausal women in Germany recruited 2002–2005 (3813 cases and 7341 age-matched controls) was used to assess the association of family history with breast cancer risk. Analysis of family history, participation in screening procedures, and tumor size regarding prognosis in patients was based on follow-up data until 2015.ResultsA first degree family history of breast cancer was associated with higher breast cancer risk (OR 1.39, p < 0.001). Patients with a first degree family history of breast cancer were more likely to have had >10 mammograms (MG) (42.7% vs. 24.9%, p < 0.001) and showed a higher rate of imaging-detected tumors (MG or ultrasound) (45.8% vs. 31.9%, p < 0.001). A smaller tumor size at initial diagnosis (below 2 cm) was more likely in patients with a positive family history (OR 1.45, p < 0.001) and a higher number of MG (≥10 MG: OR 2.29). After accounting for tumor characteristics, mammogram regularity (HR 0.72, p < 0.001) and imaging-assisted tumor detection (HR 0.66, p < 0.001) were associated with better overall survival but not with a positive family history.DiscussionPatients with a positive family history had a higher rate of imaging detected tumors with smaller size at initial diagnosis compared to patients without affected family members. Screening was associated with improved survival after a breast cancer diagnosis, irrespective of a positive family history.     

Prognostic and predictive value of TFF1 for adjuvant endocrine therapy in Chinese women with early ER positive breast cancer: Comparing aromatase inhibitors with tamoxifen

Factors that predict in favor of an aromatase inhibitors (AIs) over tamoxifen (TAM) in estrogen receptor (ER) breast cancer remains to be identified. We compared progesterone receptor (PR) and trefoil factor 1 (TTF1) status (+ve versus −ve) as predictive of superior effect of AI’s over tamoxifen among a total of 1973 Chinese women with early ER+ breast cancer. The expression of TFF1 was independently associated with ER and PR. However, there was no correlation with TFF1 and HER-2 expression. Treatment effect was more pronounced in the ER+/TFF1+ postmenopausal patients with a hazard ratio favoring AIs (HR = 0.397, 95%CI 0.183-0.860), but not in the PR positive cohorts (HR = 0.466, 95%CI 0.186-1.164). We suggested that AIs was better than TAM especially in the postmenopausal patients with ER+/TFF1+ breast cancer; however the clinical application of this observation still requires further prospective studies.     

Clinicopathologic Characteristics and Prognosis of Glycogen‐Rich Clear Cell Carcinoma of the Breast

Glycogen‐rich clear cell carcinoma (GRCC) of the breast is a rare type of breast carcinoma. Knowledge about the characteristics of this type is fragmentary, and the prognosis is on debate. In this study, we aimed to summarize the clinical, pathologic, and biologic characteristics of GRCC of the breast and analyze the survival. We reviewed the cases of breast cancer in our hospital between January 1999 and December 2009 and identified 28 patients as GRCC of the breast. The routine hematoxylin–eosin staining, periodic acid‐Schiff (PAS) staining, and diastase PAS staining were performed on the tumor tissues. The expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER‐2), Ki67 and P53 were evaluated by immunohistochemistry. Tumors with a HER‐2 score of 2+ were confirmed by fluorescent in situ hybridization test. Each GRCC case, who had complete follow‐up data, was compared with four cases of usual invasive ductal carcinomas as controls in the same database and matched with age, year of diagnosis, tumor size, nodal status, and immunophenotype. The chi‐squared test and the Fisher's exact test were used to compare the characteristics of GRCC cases and controls. The univariate analysis was used to study the prognosis, and Kaplan–Meier method was used to compare the survival of two groups. The clinicopathologic and imaging features were analyzed in the GRCC cases. Tumor sizes ranged from 0.8 to 7.5 cm (mean, 3.2 cm). Thirteen cases (46.4%) had positive lymph nodes. The positivity of ER and PR was 61.5% (16 of 26). HER‐2 was positive for three cases (12%). The positivity of Ki67 and P53 were 87.5% and 45.8%, respectively. Twenty‐four cases were followed up from 19 to 158 months. The prognosis of GRCC of the breast was significantly related with the number of positive lymph nodes (p < 0.001), and patients with more than 10 positive lymph nodes were at high risk of recurrence or metastasis. There was no significant difference in overall survival (p = 0.547), and disease‐free survival (p = 0.900) between GRCC of the breast and the usual invasive ductal carcinomas. GRCC of the breast may not have a worse survival.     

Breast Cancer in Chinese Women Younger than Age 40: Are They Different from Their Older Counterparts?

Background  Breast cancer in young women is uncommon, but when it does occur it has been reported to have aggressive biological characteristics. The incidence of breast cancer peaks at age 40 in Hong Kong Chinese women, earlier than in Caucasians. This study is the first to report the tumor characteristics and management of breast cancer in Chinese women younger than age 40 and a comparison with their older counterparts. Materials and methods  Demographic and clinicopathologic findings of 1,485 Chinese women with breast cancer seen during the period September 2003 to November 2006 were prospectively recorded, and comparisons were made between those who were under the age of 40 and those 40 years of age and older. These results were then compared with a reference population obtained from the Surveillance, Epidemiology and End Results (SEER) database between 2003 and 2004. Results  17.6% of the women were younger than 40 years old, and age distribution was significantly different from women in the SEER database. The mean age at menarche was lower in women under age 40 (p < 0.0005), and age at first live birth was also higher (p = 0.017). The rate of first detection by screening mammography was significantly higher among women who were 40 of age and older (p = 0.002). Breast conservation surgery was more commonly performed in the younger age group of Chinese women, particularly when tumor size was less than 2 cm (p = 0.001). A significantly higher proportion of women under age 40 had breast reconstruction (p < 0.001). The majority of women presented with stage 0-II disease, but in the Chinese groups the younger patients presented at a later stage (p = 0.04). Younger women had higher pathological grade and poorly differentiated tumors (p = 0.02), more nodal involvement (p = 0.024), and lymphovascular permeation involvement (p < 0.001). The majority of tumors were ER and PR positive in both groups, but younger women had a higher proportion of cerbB2-positive tumors. Conclusion  Chinese women present with breast cancer at an earlier age. Younger women present with more advanced disease and more aggressive tumor characteristics. More ethnic-specific screening protocols and treatment decisions may benefit this group of patients. This work was presented as an oral presentation at International Society Surgical Week, August 2007, Montreal, Canada and awarded the Best Paper Award.     

The usefulness of CanAssist breast in the assessment of recurrence risk in patients of ethnic Indian origin

Accurate recurrence risk assessment in hormone receptor positive, HER2/neu negative breast cancer is critical to plan precise therapy. CanAssist Breast (CAB) assesses recurrence risk based on tumor biology using artificial intelligence-based approach. We report CAB risk assessment correlating with disease outcomes in multiple clinically high- and low-risk subgroups. In this retrospective cohort of 925 patients [median age-54 (22–86)] CAB had hazard ratio (HR) of 3 (1.83–5.21) and 2.5 (1.45–4.29), P = 0.0009) in univariate and multivariate analysis. CAB's HR in sub-groups with the other determinants of outcome, T2 (HR: 2.79 (1.49–5.25), P = 0.0001); age [< 50 (HR: 3.14 (1.39–7), P = 0.0008)]. Besides application in node-negative patients, CAB's HR was 2.45 (1.34–4.47), P = 0.0023) in node-positive patients. In clinically low-risk patients (N0 tumors up to 5 cms) (HR: 2.48 (0.79–7.8), P = 0.03) and with luminal-A characteristics (HR: 4.54 (1–19.75), P = 0.004), CAB identified >16% as high-risk with recurrence rates of up to 12%. In clinically high-risk patients (T2N1 tumors (HR: 2.65 (1.31–5.36), P = 0.003; low-risk DMFS: 92.66 ± 1.88) and in women with luminal-B characteristics (HR: 3.24; (1.69–6.22), P < 0.0001; low-risk DMFS: 93.34 ± 1.34)), CAB identified >64% as low-risk. Thus, CAB prognostication was significant in women with clinically low- and high-risk disease. The data imply the use of CAB for providing helpful information to stratify tumors based on biology incorporated with clinical features for Indian patients, which can be extrapolated to regions with similarly characterized patients, South-East Asia.