CDH1 germline variants are enriched in patients with colorectal cancer, gastric cancer, and breast cancer.

BACKGROUND AND AIMS: CDH1 germline variants have been linked to heritability in diffuse gastric (DGC) and lobular breast cancer (LBC). Studies have not yet assessed whether CDH1 is a cancer-susceptibility gene in other cancers. Herein, we mapped the landscape of pathogenic and likely pathogenic (P/LP) germline variants in CDH1 across various cancers and ethnicities. METHODS: We evaluated CDH1 germline P/LP variants in 212,944 patients at one CLIA-certified laboratory (Invitae) and described their frequency in 7 cancer types. We screened for CDH1 variant enrichment in each cancer relative to a cancer-free population from The Genome Aggregation Database version 3 (gnomADv3). RESULTS: CDH1 P/LP variants were identified in 141 patients, most commonly in patients with DGC (27/408, 6.6%) followed by colorectal signet-ring cell cancer (CSRCC; 3/79, 3.8%), gastric cancer (56/2756, 2%), and LBC (22/6809, 0.3%). CDH1 P/LP variants were enriched in specific ethnic populations with breast cancer, gastric cancer, CRC, LBC, DGC, and CSRCC compared to matched ethnicities from gnomADv3. CONCLUSION: We report for the first time the prevalence of P/LP CDH1 variants across several cancers and show significant enrichment in CDH1 P/LP variants for patients with CSRCC, DGC, and LBC across various ethnicities. Future prospective studies are warranted to validate these findings.

Racial differences in estrogen receptor staining levels and implications for treatment and survival among estrogen receptor positive, HER2-negative invasive breast cancers.

BACKGROUND: African American women (AAW) die more frequently from estrogen receptor (ER) positive breast cancer than European American women (EAW). We investigated the relationship between race, percent ER staining, treatment, and clinical outcomes. METHODS: Percent ER staining (weakly ER+: 1-10%, moderately ER+: 11-50%, strongly ER+: > 50%) was abstracted from pathology reports for 1573 women with ER+/HER2- invasive breast cancer treated at a single cancer center in Detroit, MI from 2010 to 2017. Clinical outcomes and tumor characteristics were obtained from the Metropolitan Detroit Cancer Surveillance System. Associations of ER levels with demographic and clinical characteristics were evaluated using logistic regression. Overall and breast cancer-specific (BCS) survival were evaluated using Cox proportional hazards models. RESULTS: AAW were more likely to have tumors with lower ER staining levels than EAW (weakly ER+: Odds ratio (OR) 2.19, p = 0.019; moderately ER+: OR 2.80, p = 0.005). Women with weakly compared to strongly ER+ tumors were less likely to receive endocrine therapy (ET) regardless of race (OR 0.79, p < 0.001). Mortality was predicted by both AA race (Overall hazard ratio (HR) = 1.72, p < 0.001; BCS HR 1.45, p = 0.08) and low (1-50%) ER (Overall HR 1.57, p = 0.083; BCS HR 2.11, p = 0.017) adjusting for clinic-pathologic characteristics. ET was associated with improved BCS survival in all women (1-50%: HR 0.11, p < 0.001; > 50%: HR 0.24, p < 0.001). CONCLUSION: The biology of ER+/HER2- tumors varies by race, although this does not appear to account for racial differences in survival. Although ET substantially reduces mortality among women with weakly ER+ tumors, these women are less likely to be treated with ET and have poorer outcomes.

Associations of race and ethnicity with risk of developing invasive breast cancer after lobular carcinoma in situ.

BACKGROUND: Lobular carcinoma in situ (LCIS) of the breast is a risk factor of developing invasive breast cancer. We evaluated the racial differences in the risks of subsequent invasive breast cancer following LCIS. METHODS: We utilized data from the Surveillance, Epidemiology, and End Results registries to identify 18,835 women diagnosed with LCIS from 1990 to 2015. Cox proportional hazards regression was used to estimate race/ethnicity-associated hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of subsequent invasive breast cancer. RESULTS: During a median follow-up of 90 months, 1567 patients developed invasive breast cancer. The 10-year incidence was 7.9% for Asians, 8.2% for Hispanics, 9.3% for whites, and 11.2% for blacks (P = 0.046). Compared to white women, black women had significantly elevated risks of subsequent invasive breast cancer (HR 1.33; 95% CI 1.11, 1.59), and invasive cancer in the ipsilateral breast (HR 1.37; 95% CI 1.08, 1.72) and in the contralateral breast (HR 1.33; 95% CI 1.00, 1.76). Black women had significantly higher risks of invasive subtypes negative for both estrogen receptor and progesterone receptor (HR 1.86; 95% CI 1.14, 3.03) and invasive subtypes positive for one or both of receptors (HR 1.30; 95% CI 1.07, 1.59). The risk of subsequent invasive breast cancer was comparable in Asian women and Hispanic women compared with white women. CONCLUSIONS: Black women had a significantly higher risk of developing invasive breast cancer, including both hormone receptor-positive and hormone receptor-negative subtypes, after LCIS compared with white counterparts. It provides an opportunity to address health disparities.

Variations in breast cancer histology and treatment patterns between the major ethnic groups of South West Sydney.

Studies in the United States and United Kingdom have demonstrated ethnic variations in breast cancer receptor status, histology, and treatment access. This study aimed to investigate whether ethnicity variation similarly exists in Australia. Patients diagnosed with breast cancer between 2006 and 2011 across all public hospitals in the South Western Sydney Local Health District were identified and patient data collected retrospectively. Logistic regression analysis was used to measure the association between various biologic and treatment parameters and ethnicity. Ethnicity was found to have an influence on age of diagnosis, histology, treatment utilization, and recurrence in breast cancer patients.

US breast cancer mortality trends in young women according to race.

BACKGROUND: Young age at diagnosis has a negative prognostic impact on outcome in patients with breast cancer (BC). In the current study, the authors sought to determine whether there is a differential effect of race and examined mortality trends according to race and age. METHODS: The Surveillance, Epidemiology, and End Results program was used to identify women aged <50 years with invasive BC diagnosed between 1990 and 2009. Multivariate regression analyses were performed to determine the risk-adjusted likelihood of survival for white and black patients. Annual hazards of BC death according to race and calendar period and adjusted relative hazards of death for white and black women stratified by age were computed. RESULTS: A total of 162,976 women were identified, 126,573 of whom were white, 20,405 of whom were black, and 15,998 of whom were of other races. At a median follow-up of 85 months, the 5-year disease specific survival rates were 90.1% for white patients and 79.3% for black patients. Annual hazards of death in white patients decreased by 26% at 5 years after diagnosis in contrast to the hazards in black patients, which decreased by only 19%. With 1990 as the referent year, the adjusted relative hazards of death in women aged <40 years in 2005 were 0.55 (95% confidence interval [95% CI], 0.46-0.66) and 0.68 (95% CI, 0.49-0.93), respectively, for white and black women. In women aged 40 to 49 years, adjusted hazards of death were 0.53 (95% CI, 0.47-0.60) and 0.78 (95% CI, 0.61-0.99), respectively, for white and black women. CONCLUSIONS: Among young women diagnosed with BC, black patients have a worse outcome compared with white patients. Mortality declines have been observed over time in both groups, although more rapid gains have been reported to occur in white women. Emphasis should be placed on improving outcomes for young patients with BC.

What common biomarkers characterize a triple-negative profile in breast cancer?

Triple-negative breast cancers are not a homogeneous subgroup. There is substantial intra-subgroup diversity in tumor biology, prognosis and treatment sensitivity. Then, these triple-negative phenotype (TNP) groups, having specific features, can be again divided into subclasses based on an added immunohistochemical markers. The challenge in treating TNP breast cancers is that they are not responsive to antiestrogens or trastuzumab secondary to negative receptor status, and as a result have a poor prognosis. Therefore, the presence or absence of supplementary markers could help predict which therapies are best suited for patients based on the pattern that their disease markers show. In this review, we will recapitulate the major supplementary biomarkers related to triple-negative breast cancer, which could give new therapeutic options.

Ethnic differences in breast cancer risk and survival: a study on immigrants in Sweden.

BACKGROUND: There are large geographic differences in breast cancer risk but whether survival differs between low- and high-risk groups is less well-established. As the survival of cancer depends on the level of healthcare and awareness of disease risks, subtle differences in cancer biology cannot be revealed in international comparisons. Instead, comparison of diverse immigrant groups in a country of uniformly accessible healthcare system should enable conclusions to be made about ethnic determinants of cancer risk and survival. MATERIAL AND METHODS: The Swedish Family-Cancer Database was used to calculate standardized incidence (SIRs) and hazard ratios (HRs) of death from female breast cancer in 12 505 and 137 547 patients diagnosed with breast cancer among immigrants and Swedes, respectively. The ratios were adjusted for age, period, region, parity, and age at first childbirth. Ordinal logistic regression analysis was used to estimate odds ratios (ORs) for the clinical TNM classes. The analyses were stratified by menopausal status and histology. Results. Turks, Southeast Asians, and Chileans had the lowest breast cancer risk (SIR = 0.44; 95% CI 0.37-0.51) and Iraqis the highest risk (1.19; 1.05-1.35), mainly due to premenopausal cancer (1.51; 1.27-1.78). The HRs for all breast cancers were between 0.98 (0.81-1.18) (low-risk Europeans) and 1.24 (0.94-1.63) (lowest-risk non-Europeans), but were not significant. No differences in survival of ductal carcinoma between immigrants and Swedes were found, while low-risk non-Europeans had a HR of 2.88 (1.37-6.08) for lobular carcinoma. Low-risk non-Europeans were diagnosed in a higher T-class (OR = 1.87; 1.21-2.87) than Swedes. CONCLUSION: We did not find any evidence that ethnic differences in breast cancer risk substantially affect the survival. The observed poor survival of some low-risk immigrants in lobular carcinoma may be related to treatment. The tendency of low-risk immigrants to present with higher T-class compared to Swedes may depend on their lower participation in the mammography screening program.

Genetic polymorphisms of CYP2E1, GST, and NAT2 enzymes are not associated with risk of breast cancer in a sample of Lebanese women.

Changes in the activity of drug metabolizing enzymes (DMEs) are potentially associated with cancer risk. This relationship is attributed to their involvement in the bioactivation of multiple procarcinogens or the metabolism of multiple substrates including an array of xenobiotics and environmental carcinogens. 326 Lebanese women of whom 99 were cancer free (controls) and 227 were diagnosed with breast cancer (cases) were included. Blood for DNA was collected and medical charts were reviewed. Three genotyping methods were employed including: (1) restriction fragment length polymorphism (RFLP) for CYP2E1*5B, CYP2E1*6, NAT2*5 and NAT2*6; (2) gel electrophoresis for GSTM1 and GSTT1; and (3) real-time PCR for GSTP1 Ile/Val polymorphism. We analyzed the relationship between genetic susceptibilities in selected xenobiotic metabolizing genes and breast cancer risk. Allele frequencies were fairly similar to previously reported values from neighboring populations with relevant migration routes. There were no statistically significant differences in the distribution of variant carcinogen metabolizing genes between cases and controls even after adjusting for age at diagnosis, menopausal status, smoking, and alcohol intake. Despite its limitations, this is the first study that assesses the role of genetic polymorphisms in DMEs with breast cancer in a sample of Lebanese women. Further studies are needed to determine the genetic predisposition and gene-environment interactions of breast cancer in this population.

Hormone receptor and HER2 status in patients with breast cancer by races in southeastern Turkey.

PURPOSE: Hormone receptor (HR) status is a prognostic factor in women with breast cancer and differs among different ethnic groups. HR status among Turkish, Kurdish and Arabic women with breast cancer living in Turkey is unknown and in this study we investigated the relationship between HR and HER2 status and race. METHODS: FA total of 648 women with breast cancer (Turkish 438, Kurdish 174, Arabic 35 and Armenian 1) living in southeastern Turkey and referred to the Department of Radiation Oncology between July 2006-July 2012 were included in the study. Patients were categorized into 4 groups according to their HR status. Estrogen receptor (ER) and progesterone receptor (PR) positive (ER+/PR+), ER positive and PR negative (ER+/PR-), ER negative and PR positive (ER-/PR+) and ER and PR negative (ER-/PR-). Human epidermal growth factor receptor 2 (HER2) status was recorded immunohistochemically (IHC) as negative (0 and 1+), and positive (3+). Statistical analysis included ER, PR, HER2, triple subtypes (combination of ER, PR and HER2), and race. RESULTS: The median age at diagnosis was 48 years (range 20-83). ER+, PR+ and HER2+ patients were 453 (70%), 470 (72.6%) and 206 (32.1%), respectively. ER+/PR+ rates among Turkish and Arabic patients were similar, but were higher than Kurdish patients (p<0.002). Triple-negative (ER-/PR-/HER2-) rates among Kurdish and Arabic patients were similar, but were higher than Turkish patients (p=0.04). CONCLUSION: Turkish, Kurdish and Arabic women with breast cancer in southeastern Turkey differed by HR status. Compared to Turkish and Arabic patients, Kurdish patients had more unfavorable prognostic factors.

21-Gene recurrence scores: racial differences in testing, scores, treatment, and outcome.

BACKGROUND: African American (AA) women experience higher breast cancer mortality than white (W) women. These differences persist even among estrogen receptor (ER)-positive breast cancers. The 21-gene recurrence score (RS) predicts recurrence in patients with ER-positive/lymph node-negative breast cancer according to RS score-low risk (RS, 0-18), intermediate risk (RS, 19-31), and high risk (RS, >31). The high-risk group is most likely to benefit from chemotherapy, to achieve minimal benefit from hormonal therapy, and to exhibit lower ER levels (intrinsically luminal B cancers). In the current study, the authors investigated racial differences in RS testing, scores, treatment, and outcome. METHODS: Tumor registry data from 3 Atlanta hospitals identified women who were diagnosed with breast cancers during 2005 through 2009. Medical record abstraction provided information on RS and other tumor/treatment factors. Statistical analyses used chi-square/exact tests and logistic regression. RESULTS: Of 2186 patients, including 1192 AA women and 992 W women, 853 women had stage I or II, ER-positive/lymph node-negative disease and, thus, were eligible for RS testing (AA = 372 [31.2%]; W = 481 [48.5%]; P < .0001); and 272 women (31.8%) received testing (AA = 76 [20.4%]; W = 196 [40.7%]; P < .0001). Tumors were distributed into the following groups according to risk: low risk (n = 133), medium risk (n = 113), and high risk (n = 26). The mean RS did not differ by race, but risk groups did (low-risk group: 46.1% vs 50% for AA women and W women, respectively; high-risk group: 15.8% vs 7.1%, respectively; P = .043). In multivariate analyses, AA race (odds ratio, 3.6) was associated independently with high risk scores. CONCLUSIONS: AA women were half as likely as W women to receive 21-gene RS testing but were 2-fold more likely to be categorized as high risk. The current data suggested that testing guidelines are not applied equivalently, testing bias may attenuate racial differences in RS, and disparate outcomes may be explained in part by differences in RS, although compliance and pharmacogenomics also may play a role.

Memorial Sloan-Kettering Cancer Center Nomogram to predict the risk of non-sentinel lymph node metastasis in Japanese breast cancer patients.

PURPOSE: Axillary lymph node dissection (ALND) remains the standard procedure for breast cancer patients with sentinel lymph node (SLN) metastasis; however, additional nodal metastasis is detected in completion ALND in only about 50% of these patients. To identify the risk of non-SLN metastasis, the Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram. Many validation studies have been performed to evaluate the accuracy of the nomogram in Western populations, but not in Asians. We conducted this study to establish the accuracy of the nomogram in a Japanese population. METHODS: The accuracy of the MSKCC nomogram for predicting non-SLN status was tested in 116 consecutive SLN-positive patients in our hospital. We then compared the findings of the source MSKCC study with those of our study. A receiver operating characteristics (ROC) curve was plotted, and the area under the curve (AUC) was calculated to assess the discriminative power. RESULTS: Despite the differences between our patients and the source population in many respects, the area under the ROC curve was 0.73, which was comparable to that obtained in the study on the source population. CONCLUSIONS: The MSKCC nomogram provides a fairly accurate predicted probability for the likelihood of non-SLN metastases. Accordingly, it served as a useful tool for our Japanese patients with SLN metastases.

The invasive lobular carcinoma as a prototype luminal A breast cancer: a retrospective cohort study.

BACKGROUND: Although the invasive lobular carcinoma (ILC) is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known. METHODS: We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8%) with ILC for comparison with 2,833 (97.2%) with the invasive ductal carcinoma (IDC), including 1,088 (37.3%) with the luminal A subtype (LA-IDC). RESULTS: The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥ T2, 59.8% vs. 38.8%, P = 0.001), a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, P < 0.001), more frequent estrogen receptor positive (90.4% vs. 64.4%, P < 0.001), progesterone receptor positive (71.1% vs. 50.1%, P < 0.001) and HER2 negative (97.5% vs. 74.6%, P < 0.001) status, and lower Ki-67 expression (10.3% ± 10.6% vs. 20.6% ± 19.8%, P < 0.001), as well as being more likely to be of the luminal A subtype (91.4% vs. 51.2%, P < 0.001). Six (7.2%) ILC and 359 (12.7%) IDC patients developed disease recurrence, with a median follow-up of 56.4 (range 4.9-136.6) months. The outcome of ILC was close to LA-IDC (HR 0.77 for recurrence, 95% CI 0.31-1.90, P = 0.57; HR 0.75 for death, 95% CI 0.18-3.09, P = 0.70) and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, P = 0.001; HR 1.50 for death, 95% CI 0.97-2.33, P = 0.07). CONCLUSIONS: ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC.

A nonsense mutation (E1978X) in the ATM gene is associated with breast cancer.

Blood relatives of patients with ataxia-telangiectasia (A-T) have an increased risk to develop breast cancer. Allelic heterogeneity has made it difficult to confirm the role of ATM, the gene mutated in A-T, for breast cancer susceptibility in the general population. We now report that a nonsense mutation, p.E1978X (c.5932G>T), is both a classical A-T mutation and a breast cancer susceptibility allele in Eastern European populations. In a case-control study from Belarus, the E1978X mutation was identified in 10/1,891 Byelorussian breast cancer cases (0.5%) compared with 1/1,019 population controls [odds ratio (OR): 5.4; 95% confidence interval (95% CI), 0.7-42.4, P = 0.1]. A second case-control study from Russia identified the E1978X mutation in two Russian and one Ukrainian cases out of 611 breast cancer patients but not in any Russian or Ukrainian controls (P = 0.1). In a third case-control study from Poland, E1978X was observed in 7/3,910 Polish breast cancer cases (0.2%) compared with 1/2,010 cancer-free population controls (OR: 3.6; 95% CI: 0.4-29.3, P = 0.4). In the combined analysis, E1978X was significantly associated with breast cancer (Mantel-Haenszel OR: 5.6, 95% CI: 1.3-21.4, P = 0.01). Taken together, this study provides first evidence for the association of a common A-T causing mutation with breast cancer in Eastern European founder populations.

Multi-omics profiling of younger Asian breast cancers reveals distinctive molecular signatures.

Breast cancer (BC) in the Asia Pacific regions is enriched in younger patients and rapidly rising in incidence yet its molecular bases remain poorly characterized. Here we analyze the whole exomes and transcriptomes of 187 primary tumors from a Korean BC cohort (SMC) enriched in pre-menopausal patients and perform systematic comparison with a primarily Caucasian and post-menopausal BC cohort (TCGA). SMC harbors higher proportions of HER2+ and Luminal B subtypes, lower proportion of Luminal A with decreased ESR1 expression compared to TCGA. We also observe increased mutation prevalence affecting BRCA1, BRCA2, and TP53 in SMC with an enrichment of a mutation signature linked to homologous recombination repair deficiency in TNBC. Finally, virtual microdissection and multivariate analyses reveal that Korean BC status is independently associated with increased TIL and decreased TGF-ß signaling expression signatures, suggesting that younger Asian BCs harbor more immune-active microenvironment than western BCs.

Understanding Disparities in Breast Cancer Care in Memphis, Tennessee.

Although significant progress has been made in improving breast cancer survival, disparities among racial, ethnic, and underserved groups still exist. The goal of this investigation is to quantify racial disparities in the context of breast cancer care, examining the outcomes of recurrence and mortality in the city of Memphis. Patients with a biopsy-proven diagnosis of breast cancer from January 1, 2002, through December 31, 2012, were obtained from the tumor registry. Black patients were more likely to have advanced (II, III, or IV) clinical stage of breast cancer at diagnosis versus white patients. Black breast cancer patients had a two times higher odds of recurrence (95% confidence interval: 1.4, 3.0) after adjusting for race and clinical stage. Black breast cancer patients were 1.5 times more likely to die (95% confidence interval: 1.2, 1.8), after adjusting for race; age at diagnosis; clinical stage; ER, PR, HER2 status; and recurrence. Black women with stages 0, I, II, and III breast cancer all had a statistically significant longer median time from diagnosis to surgery than white women. Black patients were more likely to have advanced clinical stages of breast cancer at diagnosis versus white patients on a citywide level in Memphis. Black breast cancer patients have higher odds of recurrence and mortality when compared with white breast cancer patients, after adjusting for appropriate demographic and clinical attributes. More work is needed to develop, evaluate, and disseminate interventions to decrease inequities in timeliness of care for breast cancer patients.

The BARD1 Cys557Ser variant and breast cancer risk in Iceland.

BACKGROUND: Most, if not all, of the cellular functions of the BRCA1 protein are mediated through heterodimeric complexes composed of BRCA1 and a related protein, BARD1. Some breast-cancer-associated BRCA1 missense mutations disrupt the function of the BRCA1/BARD1 complex. It is therefore pertinent to determine whether variants of BARD1 confer susceptibility to breast cancer. Recently, a missense BARD1 variant, Cys557Ser, was reported to be at increased frequencies in breast cancer families. We investigated the role of the BARD1 Cys557Ser variant in a population-based cohort of 1,090 Icelandic patients with invasive breast cancer and 703 controls. We then used a computerized genealogy of the Icelandic population to study the relationships between the Cys557Ser variant and familial clustering of breast cancer. METHODS AND FINDINGS: The Cys557Ser allele was present at a frequency of 0.028 in patients with invasive breast cancer and 0.016 in controls (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.11-3.01, p = 0.014). The alleleic frequency was 0.037 in a high-predisposition group of cases defined by having a family history of breast cancer, early onset of breast cancer, or multiple primary breast cancers (OR = 2.41, 95% CI 1.22-4.75, p = 0.015). Carriers of the common Icelandic BRCA2 999del5 mutation were found to have their risk of breast cancer further increased if they also carried the BARD1 variant: the frequency of the BARD1 variant allele was 0.047 (OR = 3.11, 95% CI 1.16-8.40, p = 0.046) in 999del5 carriers with breast cancer. This suggests that the lifetime probability of a BARD1 Cys557Ser/BRCA2 999del5 double carrier developing breast cancer could approach certainty. Cys557Ser carriers, with or without the BRCA2 mutation, had an increased risk of subsequent primary breast tumors after the first breast cancer diagnosis compared to non-carriers. Lobular and medullary breast carcinomas were overrepresented amongst Cys557Ser carriers. We found that an excess of ancestors of contemporary carriers lived in a single county in the southeast of Iceland and that all carriers shared a SNP haplotype, which is suggestive of a founder event. Cys557Ser was found on the same SNP haplotype background in the HapMap Project CEPH sample of Utah residents. CONCLUSIONS: Our findings suggest that BARD1 Cys557Ser is an ancient variant that confers risk of single and multiple primary breast cancers, and this risk extends to carriers of the BRCA2 999del5 mutation.

Prevalence of hormone receptors and HER2/neu in breast cancer cases in Jordan.

The management and prognosis of breast cancer nowadays require the evaluation of Estrogen (ER), Progesterone Receptors (PR) and HER2/neu. Ethnic variation in the expression of these receptors is well documented. The aim of this study is to determine the prevalence of ER, PR and HER2/neu among Jordanian women with breast cancer of ductal and lobular types. A retrospective analysis was performed on 267 cases of breast cancer referred for treatment at King Hussein Cancer Center, Jordan between the period of June 2003 and June 2004. Standard immune stains were used for evaluation of hormone receptors and HER2/neu. In addition, evaluation of HER2/neu was done by FISH in selected cases. Of these 267 cases, 240 (89.9%) were ductal carcinomas of various histological grades, 122 (50.8%) of which were ER-positive, 138 (57.5%) PRpositive and 42 (17.5%) HER2/neu-positive. Twentytwo (8.2%) of all cases were lobular carcinomas, 15 (68%) of which were ER-positive, 20 (90.9%) PRpositive and 3 (13.6%) HER2/neu-positive. Five (1.9%) of the total cases were of mixed lobular and ductal types, 4 (80%) of which were ER-positive, 3 (60%) PR-positive and none were positive for HER2/neu. The prevalence of hormone receptor positivity in breast cancer of Jordanian women is lower than that of the western populations and close to other populations such as the Chinese and the minor ethnic groups of Northern America (African Americans).

Variation in Contralateral Prophylactic Mastectomy Rates According to Racial Groups in Young Women with Breast Cancer, 1998 to 2011: A Report from the National Cancer Data Base.

BACKGROUND: The rate of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer has increased over the past decade, particularly for young women. This study investigates the impact of race and socioeconomic status (SES) on use of CPM. STUDY DESIGN: Using the National Cancer Data Base (NCDB), we selected 1,781,409 stage 0 to II unilateral breast cancer patients between 1998 and 2011. Trends in use of CPM by race and SES were analyzed using chi-square tests and logistic regression models. RESULTS: For women of all ages, rates of CPM increased, from 1.9% in 1998 to 10.2% in 2011 (p < 0.001), with higher rates in women ≤45 years old, rising from 3.7% in 1998 to 26.2% in 2011 (p < 0.001). Among young women, white women had the greatest increase in CPM from 4.3% in 1998 to 30.2% in 2011 (p < 0.001). In 2011, CPM rates were 30.2% for white, 18.5% for Hispanic, 16.5% for black, and 15.2% for Asian patients (p < 0.001). The gap in CPM use between white and minority patients persisted in every SES classification, geographic region, and facility type. On multivariate analysis, minority women were 50% less likely to undergo CPM than white women were. CONCLUSIONS: Young, white, breast cancer patients are twice as likely to undergo CPM compared with women in other racial groups, even after accounting for pathologic, patient, and facility factors. Variations in shared decision-making processes between women of different backgrounds may contribute to these trends, supporting the need for future studies investigating decision-making processes and decisional aids.

Minimising unnecessary mastectomies in a predominantly Chinese community.

BACKGROUND: Recent data shows that the use of breast conservation treatment (BCT) for breast cancer may result in superior outcomes when compared with mastectomy. However, reported rates of BCT in predominantly Chinese populations are significantly lower than those reported in Western countries. Low BCT rates may now be a concern as they may translate into suboptimal outcomes. A study was undertaken to evaluate BCT rates in a cohort of predominantly Chinese women. METHODS: All patients who underwent surgery on the breast at the authors' healthcare facility between October 2008 and December 2011 were included in the study and outcomes of treatment were evaluated. RESULTS: A total of 171 patients were analysed. Two-thirds of the patients were of Chinese ethnicity. One hundred and fifty-six (85.9%) underwent BCT. Ninety-eight of 114 Chinese women (86%) underwent BCT. There was no difference in the proportion of women undergoing BCT based on ethnicity. After a median of 49 months of follow-up, three patients (1.8%) had local recurrence and 5 patients (2.9%) suffered distant metastasis. Four patients (2.3%) have died from their disease. CONCLUSION: BCT rates exceeding 80% in a predominantly Chinese population are possible with acceptable local and distant control rates, thereby minimising unnecessary mastectomies.

Racial Differences in the Use and Outcome of Neoadjuvant Chemotherapy for Breast Cancer: Results From the National Cancer Data Base.

PURPOSE: To explore racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer. METHODS: The National Cancer Data Base was queried to identify women with stage 1 to 3 breast cancer diagnosed in 2010 and 2011. Chemotherapy use and rate of pathologic complete response (pCR) was determined for various racial/ethnic groups. RESULTS: Of 278,815 patients with known race and ethnicity, 127,417 (46%) received chemotherapy, and of 121,446 where the timing of chemotherapy was known, 27,300 (23%) received neoadjuvant chemotherapy. Chemotherapy, and neoadjuvant chemotherapy in particular, was given more frequently to black, Hispanic, and Asian women than to white women (P < 0.001). This difference was largely explained by more advanced stage, higher grade tumors, and a greater proportion of triple-negative and human epidermal growth factor receptor 2 (HER2)-positive tumors in these women. Of 17,970 patients with known outcome, 5,944 (33%) had a pCR. No differences in response rate for estrogen receptor (ER)/progesterone receptor (PR)-positive tumors were found, but compared with white women, black but not Hispanic or Asian women had a lower rate of pCR for ER/PR-negative, HER2-positive (43% v 54%, P = 0.001) and triple-negative tumors (37% v 43%, P < 0.001). This difference persisted when adjusted for age, clinical T stage, clinical N stage, histology, grade, comorbidity index, facility type, geographic region, insurance status, and census-derived median income and education for the patient's zip code (odds ratio, 0.84; 95% CI, 0.77 to 0.93). CONCLUSION: Neoadjuvant chemotherapy is given more frequently to black, Hispanic, and Asian women than to white women. Black women have a lower likelihood of pCR for triple-negative and HER2-positive breast cancer. Whether this is due to biologic differences in chemosensitivity or to treatment or socioeconomic differences that could not be adjusted for is unknown.