Computer Vision Identifies Recurrent and Nonrecurrent Ductal Carcinoma in Situ Lesions with Special Emphasis on African-American Women.

Although nonrecurrent and recurrent forms of ductal carcinoma in situ (DCIS) of the breast are observed, no evidence-based test can make this distinction. The current retrospective case-control study used archival DCIS samples stained with anti-phospho-Ser226-glucose transporter type 1 and anti-phosphofructokinase type L antibodies. Immunofluorescence micrographs were used to create machine learning models of recurrent and nonrecurrent biomarker patterns, which were evaluated in cross-validation studies. Clinical performance was assessed by holdout studies using patients whose data were not used in training. Micrographs were stratified according to the recurrence probability of each image. Recurrent patients were defined by at least one image with a probability of recurrence ≥98%, whereas nonrecurrent patients had none. These studies found no false-negatives, identified true-positives, and uniquely identified true-negatives. Roughly 20% of the microscope fields of recurrent lesions were computationally recurrent. Strong prognostic results were obtained for both white and African-American women. This machine tool provides the first means to accurately predict recurrent and nonrecurrent patient outcomes. Data indicate that at least some false-positive findings were true-positive findings that benefited from surgical intervention. The intracellular locations of phospho-Ser226-glucose transporter type 1 and phosphofructokinase type L likely participate in cancer recurrences by accelerating glucose flux, a key feature of the Warburg effect.

Association between tumor mutation profile and clinical outcomes among Hispanic Latina women with triple-negative breast cancer.

Triple-negative breast cancer (TNBC) represents 15%-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women. The biology of TNBC in HL women has been poorly characterized, but some data suggest that the molecular drivers of breast cancer might differ. There are no clinical tools to aid medical oncologists with decisions regarding appropriate individualized therapy, and no way to predict long-term outcomes. The aim of this study was to characterize individual patient gene mutation profiles and to identify the relationship with clinical outcomes. We collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. We analyzed the gene mutation profiles of the collected tumors and compared the results with individual patient's clinical histories and outcomes. Of 25 patients with TNBC, 24 (96%) identified as HL. Twenty-one (84%) had stage III-IV disease. The most commonly mutated genes were TP53, NOTCH1, NOTCH2, NOTCH3, AKT, MEP3K, PIK3CA, and EGFR. Compared with other international cancer databases, our study demonstrated statistically significant higher frequencies of these genes among HL women. Additionally, a worse clinical course was observed among patients whose tumors had mutations in NOTCH genes and PIK3CA. This study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could differ in HL women compared with other ethnic backgrounds. Therefore, a deeper understanding of the biological mechanisms behind NOTCH gene and PIK3CA mutations may lead to a new treatment approach.

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.

Incidence of Ductal Carcinoma In Situ in the United States, 2000-2014.

BACKGROUND: In absence of definitive molecular risk markers, clinical management of patients diagnosed with ductal carcinoma in situ (DCIS) remains largely guided by patient and tumor characteristics. In this study, we analyzed recent trends in DCIS incidence and compared them against trends in mammography use. METHODS: The Surveillance, Epidemiology, and End Results registry was queried for patients diagnosed with DCIS from 2000 to 2014 (18 registries). Joinpoint regression analyses were used to compute age- and race-stratified trends in age-adjusted incidence of DCIS. The patterns of DCIS incidence were compared against mammography utilization data from the National Health Interview Survey. RESULTS: Between 2000 and 2014, overall DCIS incidence in the U.S. population was stable (P = 0.24). Among age groups 20 to 44 years and 45 to 55 years, DCIS incidence increased by 1.3% (P = 0.001) and 0.6% (P = 0.02) per year, respectively. Although stable among white women, DCIS incidence increased among black women and women of other races by 1.6% (P < 0.001) and 1.0% (P = 0.002) per year, respectively. Mammography uptake correlated well with DCIS incidence, with the exception of women ages 40 to 49 years and black women who experienced an increase in DCIS incidence despite stagnating and decreasing mammography uptake, respectively. CONCLUSIONS: Overall DCIS incidence rates have remained stable between 2000 and 2014. However, subgroup analyses revealed an increase in incidence among both younger women and black women. IMPACT: DCIS incidence trends did not correlate with the mammography uptake patterns, suggesting that etiologic factors other than screening may be leading to an increased DCIS incidence in these groups.

Comparative prognostic analysis for triple-negative breast cancer with metaplastic and invasive ductal carcinoma.

AIMS: Triple-negative breast cancer comprises different histological subtypes, including metaplastic breast cancer (MBC) and ductal carcinomas (IDCs). The purpose of this study was to compare triple-negative MBC (TN-MBC) with triple-negative IDC (TN-IDC) in terms of survival and predictive factors. METHODS: With access to the Surveillance, Epidemiology and End Result (SEER) database, a total of 19 383 patients met the eligibility criteria. Clinicopathological characteristics were compared between groups using the χ2 test. Univariate and multivariate analyses were applied to evaluate the disease-specific survival (DSS) and overall survival (OS). Subgroup analyses summarised the hazard ratios of TN-MBC versus TN-IDC using a forest plot. RESULTS: A total of 586 patients with TN-MBC and 18 797 with TN-IDC were included in this study. Patients with TN-MBC were older and presented with larger tumour sizes, relatively rare lymph node positive disease, and had received more chemotherapy. Compared with TN-IDC, the TN-MBC group showed a significantly poorer prognosis before and after the 1:3 matched case-control analysis. Further subgroup analysis indicated that patients with TN-MBC were older, were from specific races, and those with distant metastasis and not receiving radiotherapy had worse prognosis than patients with TN-IDC in terms of DFS and OS. CONCLUSION: Our results showed that patients with TN-MBC had unique clinicopathological characteristics and poorer prognostic subtype compared with TN-IDC. This improves our understanding of the clinicopathological and prognostic features of this rare entity but also provides more convincing therapeutic guidelines for TN-MBC in patients with breast cancer.

Twenty-Five Year Trends in the Incidence of Ductal Carcinoma in Situ in US Women.

BACKGROUND: The rising incidence of ductal carcinoma in situ (DCIS) since the widespread enactment of mammography screening has been well documented. Patterns in DCIS incidence among women of various ages and across different racial and ethnic groups have not been well described. STUDY DESIGN: The Surveillance, Epidemiology, and End Results public-use data set was queried for all women aged 40 years and older diagnosed with DCIS between 1990 and 2014. Annual age-adjusted incidence rates were compared among white, black, Hispanic, and Asian-Pacific Islander women. Additionally, using mammography screening data obtained from the CDC, patterns in mammography screening over time and as they relate to DCIS incidence rates by race and ethnicity were evaluated. RESULTS: We identified 200,400 women aged 40 years or older with DCIS. Between 1998 and 2014, a period that saw flux in national breast screening guidelines, DCIS incidence rates increased in blacks, Hispanics, and Asian-Pacific Islanders, but remained relatively unchanged in whites (increase in number of DCIS diagnoses per 100,000 individuals in the population per year among blacks +0.66/p < 0.01, Hispanics +3.0/p < 0.01, Asian-Pacific Islanders +0.53/p < 0.01, and whites +0.07/p = 0.21). After accounting for age, year of diagnosis, and mammography screening rates, DCIS incidence was found to be similar between white and black women (0.8 fewer diagnoses per 100,000 individuals compared with whites; p = 0.36) but lower for Hispanic women (9.7 fewer diagnoses per 100,000 individuals compared with whites; p < 0.01). CONCLUSIONS: The DCIS incidence rates are influenced substantially by breast cancer mammography screening patterns. However, differences exist by race and ethnicity and are not fully explained by screening mammography trends alone. Consideration should be given to including race and ethnicity in determining optimal breast screening guidelines.

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.

Caveolin-1 expression as a prognostic marker in triple negative breast cancers of Asian women.

BACKGROUND: Triple-negative breast cancers (TNBCs) are defined by their lack of oestrogen receptor, progesterone receptor and epidermal growth factor receptor 2. Although heterogeneous, the majority are aggressive and treatment options are limited. Caveolin acts as tumour suppressor or promoter depending on the cancer type. AIM: In this study, we aimed to determine if the expression levels of the candidate biomarker caveolin-1 on stromal or tumour cells were associated with clinicopathological parameters and disease outcomes in TNBCs from an ethnically diverse cohort of Asian women. METHODS: Tumour specimens from 699 women with TNBC were subjected to immunohistochemical analysis of the frequency and intensity of caveolin-1 expression in tumour and stromal cells. A subset of 141 tumour samples also underwent Nanostring measurement of CAV1 mRNA. Results were correlated with clinicopathological parameters and disease outcomes. RESULTS: Expression of caveolin-1 in stromal cells was observed in 14.4% of TNBC cases. TNBCs of the basal-like phenotype (85% of samples) were significantly more likely to exhibit stromal cell caveolin-1 expression (p=0.028), as were those with a trabecular growth pattern (p=0.007). Lack of stromal caveolin-1 expression in both TNBCs and those with the basal-like phenotype was significantly associated with worse overall survival (p=0.009 and p=0.026, respectively): accordingly, increasing mRNA levels of CAV1 in TNBC samples predicted better overall survival. Caveolin-1 expression on TNBC tumour cells was not associated with clinical outcome. CONCLUSION: Stromal, but not tumoural, caveolin-1 expression is significantly associated with survival in Asian women with TNBC.

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.

Low rate of positive margins and re-excision after partial mastectomy in highly selected breast cancer patients: A Chinese single-institution experience.

A recent randomized controlled trial firstly demonstrated that cavity shaving significantly decreased the rate of positive margins and re-excision among partial mastectomy (PM) patients. However, it remains unknown whether cavity shaving should be routinely applied to Chinese breast cancer patients undergoing PM. A total of 408 PM patients undergoing 410 PMs among 1796 surgically treated breast cancer patients at Fudan University Shanghai Cancer Centre from January 2015 to June 2015 were included in our study. Data were analysed with univariate or multivariate analysis. Overall, 11 of 410 cases (2.7%) had positive margins postoperatively. Moreover, only 24.6% of the cases (P<0.05) presented with ductal carcinoma in situ (DCIS), among whom 10.0% obtained positive margins. In multivariate logistic regression analysis, presence of mammographic calcifications was significantly associated with margin positivity (P<0.05, OR=6.06, 95% CI: 1.53-23.91). In conclusion, cavity shaving during PM should not be routinely performed in Chinese breast cancer patients, particularly in highly selected cases with a low prevalence of DCIS. PM patients with preoperative mammographic calcifications were more likely to have positive margins and might benefit more from cavity shaving.

Surgical options for Chinese patients with early invasive breast cancer: Data from the Hong Kong Breast Cancer Registry.

BACKGROUND: Breast conserving surgery (BCS) is preferred for suitable candidates, while mastectomy (MTX) with reconstruction (MTX + R) is considered a better option for patients requiring MTX. In Hong Kong, the rates of BCS and breast reconstruction are relatively low. This paper aims to study the surgical options and their predictors among Hong Kong breast cancer patients. METHODS: Data is retrieved from the Hong Kong Breast Cancer Registry (HKBCR) from 2007 to 2013. A total of 4519 Stage I-II breast cancer patients who had surgical treatments were included in this retrospective study. RESULTS: Our multivariate logistic regression shows that people who were younger (age < 40 years: OR, 1.5; 95% CI, 1.1-2.1; p = 0.010), more educated (undergraduate/postgraduate: OR, 2.8; 95% CI, 1.7-4.4; p < 0.0001), never married (OR, 1.5; 95% CI, 1.1-1.9; p = 0.002), had regular mammography screening (OR, 1.5; 95% CI, 1.3-1.8; p < 0.0001), had screen-detected cancers (OR, 1.3; 95% CI, 1.0-1.6; p = 0.031), and who underwent surgery at a private medical service facility (OR, 1.8; 95% CI, 1.6-2.2; p < 0.0001) were more likely to receive BCS. In addition, people who were younger (age < 40 years: OR, 15.9; 95% CI, 6.5-39.2; p < 0.0001), more educated (undergraduate/postgraduate: OR, 26.8; 95% CI, 3.6-201.4; p = 0.001), had regular mammography screening (OR, 1.6; 95% CI, 1.1-2.3; p = 0.008), had screen-detected cancers (OR, 2.1; 95% CI, 1.4-3.3; p = 0.001), and had smaller tumor (≤ 2.0 cm: OR, 0.39; 95% CI, 0.20-0.76; p = 0.005) were more likely to have reconstruction after MTX. CONCLUSION: Chinese patients have lower BCS and breast reconstruction rate. Besides cultural difference, patient-related factors such as age, education, marital status, mammography screening, the use of private medical facilities, and clinical characteristics including smaller tumor size and peripherally located tumor were significant predictors for type of surgical treatments in Chinese women with early breast cancer.

Projecting Individualized Absolute Invasive Breast Cancer Risk in US Hispanic Women.

Background: There is no model to estimate absolute invasive breast cancer risk for Hispanic women. Methods: The San Francisco Bay Area Breast Cancer Study (SFBCS) provided data on Hispanic breast cancer case patients (533 US-born, 553 foreign-born) and control participants (464 US-born, 947 foreign-born). These data yielded estimates of relative risk (RR) and attributable risk (AR) separately for US-born and foreign-born women. Nativity-specific absolute risks were estimated by combining RR and AR information with nativity-specific invasive breast cancer incidence and competing mortality rates from the California Cancer Registry and Surveillance, Epidemiology, and End Results program to develop the Hispanic risk model (HRM). In independent data, we assessed model calibration through observed/expected (O/E) ratios, and we estimated discriminatory accuracy with the area under the receiver operating characteristic curve (AUC) statistic. Results: The US-born HRM included age at first full-term pregnancy, biopsy for benign breast disease, and family history of breast cancer; the foreign-born HRM also included age at menarche. The HRM estimated lower risks than the National Cancer Institute's Breast Cancer Risk Assessment Tool (BCRAT) for US-born Hispanic women, but higher risks in foreign-born women. In independent data from the Women's Health Initiative, the HRM was well calibrated for US-born women (observed/expected [O/E] ratio = 1.07, 95% confidence interval [CI] = 0.81 to 1.40), but seemed to overestimate risk in foreign-born women (O/E ratio = 0.66, 95% CI = 0.41 to 1.07). The AUC was 0.564 (95% CI = 0.485 to 0.644) for US-born and 0.625 (95% CI = 0.487 to 0.764) for foreign-born women. Conclusions: The HRM is the first absolute risk model that is based entirely on data specific to Hispanic women by nativity. Further studies in Hispanic women are warranted to evaluate its validity.

DcR3 gene polymorphisms are associated with sporadic breast infiltrating ductal carcinoma in Northeast Chinese women.

Decoy Receptor 3 (DcR3), also called TNFRSF6ß, is a member of the tumor necrosis factor receptor superfamily and is a soluble receptor for FasL. DcR3 is overexpressed in cancers and contributes to tumorigenesis through immune suppression and promotion of angiogenesis. We found that DcR3 is overexpressed in breast infiltrating ductal carcinoma (IDC) cells as compared with normal controls. We also conducted a case-control study analyzing associations of DcR3 polymorphisms with breast IDC risk. Subjects included 531 females with breast IDC and 592 age-matched healthy controls. Four DcR3 single nucleotide polymorphism loci with minor frequencies of more than 5% (rs3208008, rs41309931, rs2297441 and rs1291207) were genotyped using polymerase chain reaction restriction fragment length polymorphism and sequencing. Our results revealed significant differences in rs41309931genotypes and alleles (P < 0.01). Based on Haploview software analysis, the haplotype block Ars3208008 Grs41309931 Grs2297441 Ars1291207 exhibited the highest frequency, but, haplotype blocks Ars3208008 Trs41309931 Grs2297441 Ars1291207 and Crs3208008 Grs41309931 Grs2297441 Ars1291207 were associated with breast IDC risk. This study also detected associations between DcR3 gene polymorphisms and the clinicopathological features of breast IDC, including lymph node metastasis and C-erbB2, P53, estrogen receptor and progesterone receptor status. These data indicate that DcR3 gene polymorphisms are associated with sporadic breast IDC risk in Northeast Chinese females.

Genetic variants in the mTOR pathway and breast cancer risk in African American women.

The phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (mTOR) pathway has been implicated in breast carcinogenesis. However, there has been no large-scale investigation of genetic variants in the mTOR pathway and breast cancer risk. We examined 28847 single-nucleotide polymorphisms (SNPs) in 61 mTOR pathway genes in the African American Breast Cancer Epidemiology and Risk consortium of 3663 cases [1983 estrogen receptor-positive (ER+) and 1098 ER-negative (ER-)] and 4687 controls. Gene-level analyses were conducted using the adaptive rank truncated product (ARTP) test for 10773 SNPs that were not highly correlated (r (2) < 0.8), and SNP-level analyses were conducted with logistic regression. Among genes that were prioritized (nominal P < 0.05, ARTP tests), associations were observed for intronic SNPs TSC2 rs181088346 [odds ratio (OR) of each copy of variant allele = 0.77, 95% confidence interval (CI) = 0.65-0.88 for all breast cancer] and BRAF rs114729114 (OR = 1.53, 95% CI = 1.24-1.91 for all breast cancer and OR = 2.03, 95% CI = 1.50-2.76 for ER- tumors). For ER- tumors, intronic SNPs PGF rs11542848 (OR = 1.38, 95% CI = 1.15-1.66) and rs61759375 (OR = 1.34, 95% CI = 1.14-1.57) and MAPK3 rs78564187 (OR = 1.26, 95% CI = 1.11-1.43) were associated with increased risk. These SNPs were significant at a gene-wide level (Bonferroni-corrected P < 0.05). The variant allele of RPS6KB2 rs35363135, a synonymous coding SNP, was more likely to be observed in ER- than ER+ tumors (OR = 1.18, 95% CI = 1.05-1.31, gene-wide Bonferroni-corrected P = 0.06). In conclusion, specific mTOR pathway genes are potentially important to breast cancer risk and to the ER negativity in African American women.

Excising Additional Margins at Initial Breast-Conserving Surgery (BCS) Reduces the Need for Re-excision in a Predominantly African American Population: A Report of a Randomized Prospective Study in a Public Hospital.

BACKGROUND: Margin status is an important prognostic factor for local recurrence after breast conserving surgery (BCS) for breast cancer. We designed a prospective randomized trial to evaluate the effect of shave margins on positive margins and locoregional recurrence (LRR). METHODS: Patients were randomized to BCS or BCS with resection of 5 additional margins (BCS + M). Tumor margins were classified as negative [>2 mm for ductal carcinoma in situ (DCIS); >1 mm for invasive carcinoma] based on guidelines at the time of accrual. RESULTS: A total of 75 patients with stage 0-III breast cancer (76 samples) were randomized, mean age 59.6 years with median follow-up 39.5 months. Overall, 21 patients (27.6 %) had positive margins: 14 had undergone BCS and 7 BCS + M (p = 0.005). Of the 21 patients with positive margins, 19 had DCIS on final pathology (OR 7.56; 95 % CI 1.52-37.51).All patients with positive margins were offered re-excision; 11 had negative final margins after re-excision surgery. Overall, 6 patients (8.3 %) developed LRR with recurrence being more common in the BCS group when compared with the BCS + M group (17.2 vs 2.3 %; p = 0.025). CONCLUSIONS: Taking additional cavity shave margins at the time of initial excision resulted in a reduction in positive margin rate, a decrease in return to operating room for re-excision, and lower LRR.

Triple-Negative Breast Cancer in Ghanaian Women: The Korle Bu Teaching Hospital Experience.

Breast cancers that have negative or extremely low expression of estrogen receptor and progesterone receptor and non-amplification of human epidermal growth factor receptor-2 (HER2)/neu are termed triple-negative breast cancer (TNBC). The majority of TNBC tumors belong to the biologically aggressive basal subtype, and they cannot be managed with targeted endocrine or anti-HER2/neu agents. In western, high resource environments, risk factors for TNBC include younger age at diagnosis and hereditary susceptibility. Women of African ancestry in the United States and in continental Africa have higher frequencies of TNBC, prompting speculation that this risk may have an inherited basis and may at least partially explain breast cancer survival disparities related to racial/ethnic identity. Efforts to document and confirm the breast cancer burden of continental Africa have been hampered by the limited availability of registry and immunohistochemistry resources. Our goal was to evaluate the breast cancers diagnosed in one of the largest health care facilities in western Africa, and to compare the frequencies as well as risk factors for TNBC versus non-TNBC in this large referral tertiary hospital. The Korle Bu Teaching Hospital is affiliated with the University of Ghana and is located in Accra, the capital of Ghana. We conducted an institutional, Department of Pathology-based review of the breast cancer cases seen at this facility for the 2010 calendar year, and for which histopathologic specimens were available. The overall study population of 223 breast cancer cases had a median age of 52.4 years, and most had palpable tumors larger than 5 cm in diameter. More than half were TNBC (130; 58.3%). We observed similar age-specific frequencies, distribution of stage at diagnosis and tumor grade among cases of TNBC compared to cases of non-TNBC. Ghanaian breast cancer patients tend to have an advanced stage distribution and relatively younger age at diagnosis compared to Caucasian Americans and African Americans. The triple-negative molecular marker pattern was the most common subtype of breast cancer seen among this sample of Ghanaian women, regardless of age, tumor grade, or stage of diagnosis. Research into the molecular pathogenesis of TNBC may help elucidate the reasons for its increased prevalence among women with African ancestry.

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.

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.

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.