Proportion Of Breast Cancers Research Articles

The Impact of Increase in The Proportion of Early Breast Cancer Cases on Costs and Outcomes

There is a widespread belief among medical specialists in Russia, that increase in the proportion of breast cancer (BC) cases detected on early stages would lead to the substantial decrease in BC costs in the following years, thus all screening interventions are considered as cost-saving. To estimate the impact of the increase of the proportion of early BC cases on costs and outcomes for the cohort of women 50-54 years old We developed a model to assess lifelong costs and outcomes for the cohort of patients diagnosed with BC in 2014 at age of 50-54 (7,450 cases, 69.1% with stage I-II). Only direct medical costs (treatment and follow-up) of the BC covered by health care system were estimated, based on federal statistics, cancer registry data and experts’ survey. During the first year, costs and survival for the initial treatment were assessed. Then patients entered Markov model with 3 states: “progression-free”, “progression”, “death” with cycle length of 1 year. Transition probabilities were defined using published data, risk of death in “progression-free” state was assumed to be the same as in general population. At the next step, we estimated costs and outcomes if the proportion of early BC cases would increase by 1% (75 cases diagnosed at stage I-II, instead of IV). Costs and outcomes were discounted at 3,5% rate. In the basecase analysis lifelong costs per cohort were €44.04 million and outcome–60,665 life years. Increase in the proportion of early BC cases by 1% resulted in €120,414 decrease in costs during the first year, but at the lifelong horizon costs increased by €110,072, and 513 life years were gained per cohort. The improvement in the survival of BC patients due to earlier diagnosis results in higher lifelong costs, which are not compensated by the lower cost of initial cancer treatment.

Abstract A22: Racial/ethnic and insurance-based disparities in receipt of long-term follow-up care information among a population-based sample of breast and colorectal cancer patients in New Jersey

Abstract Background: Follow-up information for cancer patients transitioning from active treatment to survivorship care is important for ensuring patient engagement and appropriate care coordination. Few studies have examined whether disparities exist in the receipt of information on late and long-term effects among diverse cancer patients during the initial Affordable Care Act implementation period, a time when care quality and care coordination gained increased attention. Methods: We conducted mail surveys between September 2015 and June 2016 in a population-based sample of breast cancer (BC) and colorectal cancer (CRC) cases from the New Jersey State Cancer Registry to understand cancer care experiences. We included cases diagnosed in 2012-2014. Sampling was stratified by age (21-64 years vs. > 64 years) and oversampled for cases with Medicaid coverage or uninsured at the time of diagnosis. We examined overall patient-reported responses about receiving follow-up care information and also whether receipt of follow-up information differed by race/ethnicity or insurance type. Significant differences between groups were determined at p <0.05 level using chi-squared and t-tests. Results: A total of 180 breast and 60 colorectal cancer cases participated in the study. Approximately 13% of cases were Hispanic, 7% non-Hispanic black, and 68% non-Hispanic white. At the time of diagnosis, 14% of BC and 22% of CRC patients were uninsured. A high proportion of breast cancer (84%) and colorectal (77%) cancer cases received detailed information from their cancer care provider about the need for regular follow-up care and monitoring post-treatment. Similarly, high proportions (96% and 90%) of BC and CRC patients, respectively, received written instructions on when to return for checkups. A much smaller proportion of patients of both cancer types combined reported receipt of written summaries of their cancer treatment (42%), detailed discussion with their providers about the late or long-term effects of treatment (58%) or lifestyle and health recommendations (54%). We observed significant differences in the receipt of follow-up information by insurance status but not race/ethnicity. For example, having a detailed discussion of the late or long-term side effects from treatment with providers were lower among uninsured (49%) and Medicare patients (54%) compared to privately-insured (64%) and Medicaid patients (71%). Similarly, a higher proportion of uninsured patients (34%) and Medicaid patients (30%) did not discuss the emotional of social needs related to their cancer treatment at all with their doctor compared to a lower proportion of privately-insured patients (25%). Conclusions: Our findings from a diverse population-based sample of recently diagnosed BC and CRC cases provide insight on patient reported experiences of care during the initial Affordable Care Act implementation period. Although it is reassuring that the majority of patients received information about the need for regular follow-up and when to return for check-ups, it is alarming that roughly half of the participants in our sample did not get a summary of their treatment or detailed information from their doctor about the long-term effects of their care. These results suggest the need to improve care coordination and follow-up efforts among specific disadvantaged subgroups, particularly in settings serving uninsured or underinsured groups. Policy and intervention efforts should focus on addressing how to better coordinate care between oncologists and primary care providers, particularly for underserved cancer patients, as the number of cancer survivors continue to grow nationally. Citation Format: Jennifer Tsui, Antoinette M. Stroup, Carolina Lozada, David Rotter, Natalia L. Herman, Dirk F. Moore, Grace L. Lu-Yao. Racial/ethnic and insurance-based disparities in receipt of long-term follow-up care information among a population-based sample of breast and colorectal cancer patients in New Jersey. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A22.

Invasive Ductal Carcinoma: Correlation of Immunophenotypic Features with Age.

To evaluate the frequency of hormone receptors and Her2neu expression and their correlation with age in patients of carcinoma breast. Descriptive, cross-sectional study. Department of Histopathology, Dr. Ziauddin Hospital, Karachi, between the period 2006 - 2013. Estrogen receptors, progesterone receptors and Her2neu immunohistochemical staining was performed on all specimens of carcinoma breast of female patients. Allred scoring was followed using normal epithelium as internal control. Age was determined in years. Results were described as percentages. Three hundred and forty-six cases of infiltrating ductal carcinoma of breast between the age of 20 - 90 years (mean= 49 ±14 years) were studied. Seventy-nine (23%) cases were below the age of 40 years. ER +ve cases were 210 (61%), PR +ve were 190 (55%), and 78 (23%) were Her2neu +ve. Three were 12 (3%) triple positive cases and 58 (17%) triple negative cases. One hundred and seven (31%) cases were ER/PR+ve and Her2neu -ve. Most of the breast cancer cases were aged between 41 - 50 years. Estrogen receptor positivity was maximum between 41 - 60 years. Fifty percent cases of carcinoma breast below 30-year age were also ER positive. A high proportion of breast cancer in young Pakistani females is alarming. Younger age harbours aggressive clinicopathologic characteristics. There is a due need for identifying high risk individuals/families including BRCA1 and BRCA2 testings, biologically driven trials devoted specifically to this group.

Molecular Testing in Breast Cancer: A Guide to Current Practices.

-Molecular diagnostics play a role in the management of many cancers, including breast cancer. -To provide an update on molecular testing in current clinical practice, targeted at practicing pathologists who are not breast cancer specialists. -This study is a narrative literature review. -In addition to routine hormone (estrogen and progesterone) receptor testing, new and recurrent tumors are tested for HER2 amplification by in situ hybridization or overexpression by immunohistochemistry. Intrinsic subtyping of tumors represents a fundamental advance in our understanding of breast cancer biology, but currently it has an indirect role in patient management. Clinical next-generation sequencing (tumor profiling) is increasingly used to identify potentially actionable mutations in tumor tissue. Multianalyte assays with algorithmic analysis, including MammaPrint, Oncotype DX, and Prosigna, play a larger role in breast cancer than in many other malignancies. Given that a proportion of breast cancers are familial, testing of nontumor tissue for cancer predisposition mutations also plays a role in breast cancer care.

Analysis of the Incidence of the Female Population Omsk Region with Breast Cancer for Ten Years of (2003 - 2012)

The paper presents the epidemiological characteristics of diseases of the female population of the Omsk region of breast cancer (BC) from 2003 to 2012, Determined the dynamics of morbidity. A comparative analysis of breast cancer incidence rates in urban and rural residents of the area. In the structure of malignant tumors of the female population of the Omsk region the proportion of breast cancer was 23.3% and was lower than the national average (20.0%). In rural areas, compared with the regional center had higher growth rates of incidence of breast cancer (1.5-fold).

Abstract P6-10-08: Pregnancy associated breast cancer (PABC); no evidence of patients' or doctors' delays

Abstract Background: A small, but not negligible, proportion of breast cancers in young women are detected in association with childbearing. While pregnancy usually is a period of intense medical observation, signs and symptoms of a malignancy may be overlooked or misinterpreted as pregnancy-related, resulting in diagnostic and treatment delays. Also, a delayed diagnosis in pregnant women has been suggested as a reason for the more advanced disease and poorer outcomes in women with pregnancy-associated breast cancer. Material and Methods: For the purpose of the present study, pregnancy-associated breast cancer (PABC) was defined as an invasive breast tumor diagnosed during pregnancy and up to two years post-delivery (non-PABC cases were diagnosed outside this time window, or nulliparous). Based on a systematic review of medical records for women aged 15-44 years at diagnosis with PABC and non-PABC identified in Swedish health care registers, chart information was retrieved by trained nurses for a total of 570 women (285 PABC women and 285 age and hospital matched non-PABC women) treated at 11 hospitals across Sweden between 1992 and 2009. Median waiting times from initial signs or symptoms in days to start of treatment, and time periods within, were computed using the Kaplan-Meier method and compared using the logrank test for the Kaplan-Meier curves. Dates on first symptoms were available for 122 matched PABC/non-PABC pairs, in total 244 patients. Full dates to assess and compare times between first health care contact – diagnosis – start of treatment, were available for 246 PABC/non-PABC pairs, in total 492 women. Objective: To examine and compare lengths of several defined waiting times within the time period from initial symptoms to start of treatment in women diagnosed with PABC and non-PABC. Results: Patient delay-time between first symptom and first point of contact with health care provider. Median time between first symptoms and first contact with health care was 36 days and 45 days for women with PABC and non-PABC, respectively (logrank test p-value 0.48). Time between first health care contact and diagnosis Median time between first contact and diagnosis was 7 days for both PABC and non-PABC women (logrank test p-value 0.16). Time between diagnosis and start of treatment The median waiting time from date of diagnosis to initiation of treatment was shorter in women with PABC (22 days) compared to non-PABC women (26 days) (logrank test p-value 0.14). Time between first contact and start of treatment The median delay of start of treatment from first contact with a health care provider was 34 days in PABC women and 37 days in non-PABC women. (logrank test p-value 0.14). Conclusions: Patients' delay and the time between first contact with health care and start of treatment was shorter in women with PABC compared to non-PABC. Taken together, the present results do not support the notion that diagnostic and treatment delays are more common in women diagnosed with breast cancer during or shortly after pregnancy. Citation Format: Lambe M, Fredriksson I, Johansson ALV. Pregnancy associated breast cancer (PABC); no evidence of patients' or doctors' delays. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-08.

Abstract P6-02-06: Ductal carcinoma in situ and breast cancer screening in Japanese breast cancer registry

Abstract Background: There is an increasing trend in the rate of breast cancer screening for women in all ages in Japan. While screening leads to early cancer detection and improved treatment outcome, it may lead to over-treatment of potentially benign tumors. Little is known about the biological differences between screen- and self-detected cancers. Method : To compare the biological characteristics of breast cancers by the mode of detection, we used the data from Japanese Breast Cancer Registry (JBCR), a nation-wide registry of newly diagnosed breast cancer cases in Japan. We enrolled into the study cohort female patients who underwent surgical resection of their breast cancers during the period between January 1st 2004 and December 31st 2011, whose mode of cancer detection were recorded in the registry. We compared the clinico-pathological features of the tumors including histological classifications, estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status, and TNM stages between screen- and self-detected cases. Also, we assessed the yearly trend in the proportion of screen-detected cases over the study period. Results: We identified 205,544 patients matching the inclusion criteria within the registry. In total, 31.8% (65,358 / 205,544) of cases were detected by screening. Cases detected by screening were more likely to have favorable prognostic features than those self-detected: (DCIS: screening 19.8% vs self-detection 4.1%, node negative: 77.0% vs 61.6% and ER positive: 82.0% vs 72.9%, respectively). On the contrary, self-detected tumors were more likely to have poor prognostic characteristic (HER2 positive: screening 11.7% vs self-detection 14.0%, T3 or T4: 2.1% vs 9.8, respectively). All these findings reached statistical significance (p-value < .001). Over the years, the proportion of breast cancers detected by screening among all cases increased from 21.7% in 2004 to 37.1% in 2011. During the same time period, among the all treated DCIS, the proportion of screen-detected DCIS increased from 41.5% to 66.0% and that of ER positive cancers also increased from 23.2% to 39.7%. Interpretation: This study using JBCR demonstrated that DCIS tumors account for a substantial proportion of screen-detected cancers. The distributions of biological characteristics in screen-detected cancers differ from those observed in self-detected cancers. This may account in part for the favorable prognostics of screen-detected cases. Citation Format: Iwamoto T, Kumamaru H, Miyata H, Tomotaki A, Niikura N, Kawai M, Anan K, Hayashi N, Masuda S, Tsugawa K, Aogi K, Ishida T, Masuoka H, Iijima K, Matsuoka J, Doihara H, Kinoshita T, Nakamura S, Tokuda Y. Ductal carcinoma in situ and breast cancer screening in Japanese breast cancer registry. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-02-06.

Abstract P5-14-06: Lapatinib reverses endocrine resistance in select patients with HER2 negative, hormone positive metastatic breast cancer

Abstract Introduction: A significant proportion of breast cancer (BC) patients show primary or acquired resistance to endocrine therapy (ET). The cross-talk between estrogen receptor and other growth factor receptor (GFR) families is suggested to play a crucial role in the development of endocrine resistance and dual targeting of these pathways can potentially reverse endocrine resistance. Lapatinib (Lap) is an oral, dual inhibitor of EGFR/HER2 and preclinical studies have demonstrated combination of Lap and ET to be effective in setting of endocrine resistance. Aims: 1) To evaluate if Lap can restore efficacy of aromatase inhibitor (AI) or fulvestrant(F) in metastatic BC, 2) Study blood/tissue response biomarkers. Methods: Eligible patients with HER2 negative (IHC and FISH) hormone positive metastatic BC who had progression of disease while on AI or Fulvestrant (+/-AI), or developed metastatic disease on adjuvant AI were enrolled on an IRB approved phase II study. Study treatment included continuation of same dose and schedule ET on which last progression was noted with the addition of Lapatinib 1500 mg PO/QD. Patients could have unlimited prior ET. The study end points included clinical benefit rate (CBR) at 16wks (CBR16), CBR at 24 wks (CBR24) and PFS. Correlative studies included blood markers (HER2/ECD, CTC, CTC HER2 phenotyping) and tumor next generation sequencing (NGS) (315 cancer-related genes, Foundation Medicine, Inc). Results: Between 2009 and 2014, thirty-two patients were enrolled. Median age: 61.5 yrs, median number of prior endocrine regimens: 2 (range 1-4), 72% had visceral disease, 28% had bone only disease, 67% were considered to be responsive to the last ET. For 28 patients evaluable for efficacy the ET was AI =29%, F= 32%, AI+F=39%. The CBR16 was 25% (7/28) and the CBR24 was 14%(4/28). Median PFS for the entire cohort was 2.1 mths and the median PFS for patients with CB at 16 weeks was 7.4 mths. 12% of patients had Grade 3/4 AE (Diarrhea: 6%, Vomiting: 6%, Rash: 3%). Serum HER2/ECD was elevated in 43%, >1 CTC detected in 57%, HER2 positive CTC noted in 18%. HER2/ECD and HER2 positive CTC did not correlate with CBR16. Tumor NGS done on partial sample set (n=7, patients without early progression) demonstrate PI3K pathway activating mutations in 55% (4/7) of patients (PIK3CA mutations=3, AKT3 amplification & PTEN homozygous deletion=1). No ESR1 alterations were observed. All 4 patients with PIK3CA pathway mutations demonstrate CB at 16 wks, and 3/4 demonstrate CB at 24 wks. Conclusion: Addition of Lap restored sensitivity to ET (AI/Fulvestrant) in 25% of patients with HER 2 negative BC. Response was independent of HER 2 positive CTC and HER2/ECD levels. Genomic profiling suggests a relationship between PIK3CA mutation and benefit from this approach. NGS of the entire study cohort is in process and will be reported. HER2-negative breast cancers harboring PIK3CA mutations may rely more on GFR/PI3K signaling than on estrogen for growth; thus, blocking GFR signaling with lap might restore hormonal sensitivity. A randomized study of lap + ET in selected patients with HER2 negative BC is warranted and biomarker results from this study may help identify subgroups that should be targeted in a larger study. Citation Format: Sharma P, Kimler BF, Ward C, Wang K, Ali S, Balasubramanian S, O'Dea AP, Madhusudhana S, Baccaray S, Fabian CJ, Schmitt SB, Godwin AK, Khan QJ. Lapatinib reverses endocrine resistance in select patients with HER2 negative, hormone positive metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-14-06.

Contribution of BRCA1 and BRCA2 Germline Mutations to Early Algerian Breast Cancer.

Breast cancer is the most common female malignancy and the leading cancer mortality cause among Algerian women. Germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast cancer have not been clearly identified within the Algerian population. It is necessary to study the BRCA1/2 genes involvement in the Algerian breast cancer occurrence. We performed this study to define germline mutations in BRCA1/2 and their implication in breast cancer among young women from eastern Algeria diagnosed or treated with primary invasive breast cancer at the age of 40 or less who were referred to Anti-Cancer Center of Setif, Algeria. Case series were unselected for family history. Eight distinct pathogenic mutations were identified in eight unrelated families. Three deleterious mutations and one large genomic rearrangement involving deletion of exon 2 were found in BRCA1 gene. In addition, four mutations within the BRCA2 gene and one large genomic rearrangement were identified. Novel mutation was found among Algerian population. Moreover, five variants of uncertain clinical significance and favor polymorphisms were identified. Our data suggest that BRCA1/2 mutations are responsible for a significant proportion of breast cancer in Algerian young women.

Abstract A43: Population attributable risk of postmenopausal breast cancer according to known and modifiable breast cancer risk factors

Abstract Introduction: Multiple risk factors for postmenopausal breast cancer are well established. We aimed to determine the proportion of breast cancers in the population that are attributable to established risk factors, and to different combinations of risk factors, to better understand the proportion of breast cancer which could be prevented by changes in modifiable risk factors. Methods: We used data from the Nurses' Health Study (NHS), an ongoing prospective study of 121,700 US nurses initiated in 1976. Information on breast cancer risk factors and breast cancer diagnosis is collected every two years through mailed questionnaires. Follow-up for this cohort of women through 2008 has been greater than 90%. The analysis was restricted to postmenopausal women. Relative risks and their 95% confidence intervals were estimated by Cox models stratified by calendar year and age in months at the time of each questionnaire return using the counting process data structure to facilitate the incorporation of time-varying covariates. We included the following established breast cancer risk factors in the analyses: age, age at menarche, height, age at first birth/parity, current adult BMI/weight change since age 18, alcohol consumption, physical activity, breast feeding, menopausal hormone therapy, family history of breast cancer, and prior benign breast disease. Full and partial population attributable risk percents (PARs) were calculated. We conducted analyses for total invasive breast cancer, estrogen receptor (ER)+, and ER- breast cancer. Results: Over the course of follow-up, 8,421 postmenopausal invasive breast cancer cases developed over 2,424,778 person years between 1980 and 2008. As expected, earlier age at menarche, increasing weight gain since age 18, increasing alcohol consumption, current use of menopausal hormones, and being tall were all significantly positively associated with risk of breast cancer in multivariate models. Because age has a large influence on the risk of breast cancer we estimated the PAR both with and without age. When all of the risk factor variables except for age were include in the model the PAR for all invasive breast cancers was 0.62 (95% CI 0.46-0.75). Thus, if women could change to the lowest risk category for all of the variables considered, the number of invasive breast cancers would be reduced by 62%. In models that additionally included age, the PAR was 0.92 (95%CI 0.76-0.97) for total invasive and 0.95 (95%CI 0.75-0.99) for ER+ breast cancer and 0.86 (95%CI 0.21-0.98) for ER- breast cancer. However, because many of the risk factors considered are not easily modifiable, we also examined more readily modifiable risk factors singly and in combinations. The risk factor with the largest PAR, was BMI/weight gain since age 18 (PAR=0.24(95%CI 0.13-0.34)). Reproductive risk factors such as age at first birth/parity (PAR=0.10 (95%CI 0.07-0.14)) and age at menarche (PAR=0.08 (95%CI 0.03-0.12)) also had modest impact on the PAR, both of which were higher for ER+ breast cancer than ER- breast cancer. When considering all of the modifiable risk factors together we found that changing one's risk factor profile to have the lowest weight gain, no alcohol consumption, high physical activity, breast feeding and no hormone use was associated with a PAR of 0.38 (95%CI 0.23-0.52) for overall invasive breast cancer. Conclusion: The established breast cancer risk factors explain a large proportion of both ER+ and ER- postmenopausal breast cancers in the population. The most important modifiable risk factor for postmenopausal breast cancer prevention is maintaining a healthy weight. Citation Format: Rulla M. Tamimi, Molin Wang, Mathew Pazzaris, Stephanie A. Smith-Warner, Walter C. Willett, A. Heather Eliassen, Donna Spiegelman, David J. Hunter. Population attributable risk of postmenopausal breast cancer according to known and modifiable breast cancer risk factors. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A43.

Abstract B79: Trends in mammography quality benchmarks met over time: Moving beyond the Mammography Quality Standards Act to address breast cancer disparities

Abstract Backround: In 2007, the Metropolitan Chicago Breast Cancer Taskforce (The Taskforce) was initiated to identify the reasons for an alarming Black/White breast cancer mortality gap in metropolitan Chicago and to propose solutions. One hypothesis raised was that unequal access to high quality breast cancer screening and treatment care may be a significant driver of Chicago's breast cancer disparity. While there is growing interest in the role of breast cancer screening quality in explaining black/white breast cancer mortality gap, there is no research to our knowledge assessing quality measures about the breast cancer screening processes within facilities across the state of Illinois. We summarize data and report trends on 11 breast cancer screening metrics from 3 years of mammography quality data surveillance for facilities in Illinois. Methods: The Taskforce collected aggregate data on 11 breast cancer screening quality metrics for calendar years 2006, 2009, and 2011, including the number of screening mammograms that: received follow-up imaging within 30 days and 12 months; received a biopsy recommendation within 12 months of the screen; resulted in a biopsy recommendation within 12 months; resulted in a biopsy (following recommendation) within 60 days and 12 months of the screen, respectively. Finally, we requested the number of cancers diagnosed within 12 months of an abnormal screening mammogram and the number of these that were minimal and early stage cancers. Data were analyzed for the 32 facilities that submitted metrics across all 3 years. The change in the mean number of benchmarks met was estimated using linear regression using a generalized estimating equations approach with exchangeable correlation matrix and robust standard errors to account for clustering by site. At each time point 95% confidence intervals were estimated. Results: Out of 11 possible metrics, the average number of benchmarks met by each facility for 2006, 2009 and 2011 was 4.88, 7.06 and 8.09, respectively. This represented a 0.65 increase in the overall mean number of benchmarks met by calendar year (95%CI=0.44, 0.75) (or an overall 1.61 increase in the overall mean number of benchmarks met per time point, 95%CI=1.16, 1.97). With respect to individual benchmarks, the proportion of facilities able to show that they met the benchmarks increased substantially between 2006 and 2011 for many benchmarks including cancer detection rate (0.66 to 0.91, p=0.008), proportion of breast cancers diagnosed as minimal (0.28 to 0.88, p=0.0000) and early stage (0.22 to 0.66, p=0.000). Other benchmarks remained unmet by a majority of facilities despite showing substantial improvement over time. These included timely imaging within 30 days of the screen (0.28 to 0.44, p=0.077), and timely biopsy within 60 days of the screen (0.13 to 0.42, p=0.002). Discussion: The American College of Radiology recommends that facilities meet certain additional quality benchmarks above and beyond the audit requirements of the Mammography Quality Standards Act. These include measuring the proportion of abnormal screening mammograms, timeliness of follow-up, extent of screen-detection (i.e., cancer detection rate for screening mammograms), and ability to detect small and early stage tumors. To date, none of these recommendations have been incorporated into MQSA guidelines. The results of this quality improvement project show an overall improvement across time in the average number of quality benchmarks institutions can demonstrate that they meet. Much of this improvement likely stems from an increased ability to collect and report the data needed to construct these measures. Lack of timeliness of diagnostic imaging and biopsy services remain a clear shortcoming for many facilities. Citation Format: Katherine Y. Tossas-Milligan, Bethliz Irizarry, AnneMarie Murphy, Garth H. Rauscher. Trends in mammography quality benchmarks met over time: Moving beyond the Mammography Quality Standards Act to address breast cancer disparities. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B79.

5-Carboxylcytosine levels are elevated in human breast cancers and gliomas.

BackgroundDNA methylation (5-methylcytosine (5mC)) patterns are often altered in cancers. Ten-eleven translocation (Tet) proteins oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). In addition to their presumptive specific biological roles, these oxidised forms of 5mC may serve as intermediates in demethylation process. According to several reports, 5hmC levels are strongly decreased in cancers; however, the distribution of 5fC and 5caC in malignant tissue has not been studied.FindingsHere, we examine the levels of 5hmC and 5caC in 28 samples of normal breast tissue, 59 samples of invasive human breast cancer and 74 samples of gliomas using immunochemistry. In agreement with previous reports, we show that 71 % of normal breast samples exhibit strong 5hmC signal, compared with only 18 % of breast cancer samples with equivalent levels of 5hmC staining. Unexpectedly, although 5caC is not detectable in normal breast tissue, 27 % of breast cancer samples exhibit significant staining for this modification (p < 0.001). Surprisingly, the presence of immunochemically detectable 5caC is not associated with the intensity of 5hmC signal in breast cancer tissue. In gliomas, we show that 5caC is detectable in 45 % of tumours.ConclusionsWe demonstrate that, unlike 5hmC, the levels of 5caC are elevated in a proportion of breast cancers and gliomas. Our results reveal another level of complexity to the cancer epigenome, suggesting that active demethylation and/or 5caC-dependent transcriptional regulation are pre-activated in some tumours and may contribute to their pathogenesis. Larger studies to evaluate the clinicopathological significance of 5caC in cancers are warranted.

Prognostic features of breast cancer differ between women in the Democratic Republic of Congo and Belgium

ObjectivesCompared to European women, breast cancers in African women present at a younger age, with a higher tumor grade and are more often estrogen receptor (ER)/progesterone receptor (PR) negative. We here investigate the histopathological and immunohistochemical characteristics (ER, PR and human epidermal growth receptor 2 (HER2)) and the proportion of triple negative (Tneg) invasive breast cancers from an unselected series of patients diagnosed in Kinshasa, and compare them to a population of Caucasian women with a palpable breast cancer. Materials and methodsFrom 2010 till 2013, during the first breast cancer awareness campaign, organized in Kinshasa, 87 patients were diagnosed with invasive breast cancer. Diagnose was based on core biopsy. The control group consisted of Caucasian women (University Hospitals of Leuven, Belgium) with a palpable mass, diagnosed between 2000 till 2009, treated with surgery of which the histopathological and immunohistochemical characteristics were collected on excision specimens. Each patient in the Kinshasa group was matched based on age and tumor size to one or more patients of the Leuven database. Differences between both groups with respect to hormone receptors (ER, PR, HER2, Tneg) or grade are presented as relative risks (RR). The analysis is based on a log-binomial model accounting for clustering through matching by a random intercept for cluster. Differences between both groups with respect to hormone receptors correcting for grade is performed by the inclusion of grade as a covariate in the model. ResultsAfter adjusting for age, tumor volume and tumor grade, ER was more frequently negative (RR = 0.71, p < 0.001), with a trend in the same direction for PR (RR = 0.87, p = 0.057), and HER2 more often positive (RR = 1.60, p = 0.015) compared to the group from the University Hospitals of Leuven. There was no difference in the proportion of breast cancers being triple negative. Sub-analysis showed that the higher HER2 positive rate was only observed in older patients (≥50y: RR = 2.07, p = 0.007) whereas no difference in HER2 positive rate was found in younger patients (<50y: RR = 1.30, p = 0.358). A higher ER negative rate was observed in both age groups, however more pronounced in older patients (≥50y: RR = 0.64, p = 0.001; <50y: RR = 0.79, p = 0.018). ConclusionBreast cancer in women of Kinshasa presents at younger age and is more aggressive (more frequently ER negative and HER2 positive) compared to Caucasian women and this is more pronounced in older women (>50y). Only the ER results were concordant with the results of two similar studies (comparing an African with a European group), but were different when compared to studies on African-American women with breast cancer. This information is very important considering the treatment option: as more tumors are ER negative, endocrine therapy cannot be given while chemotherapy is often too expensive.

Thyroid hormone receptor α in breast cancer: prognostic and therapeutic implications.

We determined the expression of two transcriptional variants of thyroid hormone receptor alpha (THRα1 and THRα2) in samples from a cohort of breast cancer patients and correlated expression levels with survival. 130 women who were diagnosed with invasive breast carcinoma between 2007 and 2008 were included. Representative sections of their tumours were analyzed in triplicate on a tissue microarray for expression of THRα1 and THRα2 by immunohistochemistry. The prognostic significance of THRα1 and THRα2 expression was assessed using Kaplan-Meier survival analyses, adjusted for known prognostic factors. Seventy-four percent of tumours had high expression of THRα1 (Allred score ≥6) and 40 % had high expression of THRα2. Expression of THRα2 correlated positively with ER expression (p < 0.001) and with PR expression (p < 0.001), but negatively with HER2 expression (p = 0.018). Patients with low THRα2 expression had inferior 5-year overall survival (75.3 %) compared to those with high expression (91.7 %; p = 0.06). In a multivariate model, high THRα2 expression was a significant and independent prognosticator of improved overall survival (HR = 0.84; 95 % CI 0.71-0.98). Many breast tumours express THRα2 at high levels and these patients experience improved survival. Thyroid hormone signalling may be important in a proportion of breast cancers and THRα2 expression may be a regulator of signalling in this pathway.

PB.41. What is the incidence of internal mammary node lymphadenopathy on CT in primary breast cancer patients within 1 year of a diagnosis?

The importance of internal mammary nodes (IMNs) in the staging and treatment of breast cancer patients is controversial. Lymphoscintigraphic studies have demonstrated that a significant proportion of breast cancers have primary or partial IMN drainage. However, historical studies demonstrated no overall benefit of treating IMNs with either surgery or radiotherapy. But with recent advances in treatment, targeted radiotherapy of the IMN chain is now possible. Thus we sought to establish the frequency of IMNs within our primary breast cancer population.

Breast cancer subtypes in Chinese Americans: A study from the Mount Sinai Health System.

39 Background: Breast cancer has been increasing in many Asian countries, as well as among Asian Americans. While many studies have examined breast cancer subtypes in African American and Caucasian populations, few have looked at tumor subtypes in the Asian population. We aimed to examine breast cancer subtypes in Chinese Americans. Methods: We identified all Chinese patients diagnosed with invasive breast cancers between 2005 and 2012 from the Cancer Registry of Mount Sinai Beth Israel, Mount Sinai St. Luke’s, and Roosevelt Hospitals. The following clinical data were collected for each patient: age at diagnosis, year of diagnosis, largest tumor size (cm), lymph node status, estrogen receptor (ER), progesterone receptor (PR) and HER2 status. Based on ER, PR, and HER2, patients were categorized into three molecular subtypes: 1) Hormone receptor (HR)+ (ER and/or PR positive, HER2 negative), HER2+ and triple negative (TN) (ER, PR, and HER2 negative). Descriptive variables were analyzed using one-way Anova test. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from logistic regression models. Results: There were 175 Chinese patients diagnosed with invasive breast cancers from 2005 to 2012. Median age at diagnosis was 54 (range 27-90). One hundred fourteen (65%) were HR+, 41 (23%) were HER2+, and 20 (11%) were TN. There were 59 (34%) patients diagnosed at age ≤ 50 and twelve patients (7%) were diagnosed at age &lt; 40. There were more HER2+ and TN breast cancers diagnosed in women age ≤ 50 compared to age &gt; 50, but the difference was not statistically significant. Women in the HR+ group were diagnosed at an older age compared to the other two subgroups (57 ± 12, 52 ± 8, and 52 ± 10 for HR+, HER2+, and TN, respectively, p = 0.036). Patients with TN breast cancers were more likely to have lymph node involvement compared to HR+ or HER2+ patients (p = 0.02). There was a trend of increasing prevalence of HER2+ breast cancer observed in recent years: 18.5% in 2005-2006, 23.8% in 2007-2008, 18.4% in 2009-2010, and 29.8% in 2011-2012. Conclusions: We observed a high proportion of breast cancer among young Chinese Americans as well as an increasing prevalence of HER2+ breast cancer in this population in recent years. Further studies are warranted.

Retrospective analysis of clinicopathological factors and outcome in breast cancer in young women in a tertiary care hospital in India.

The proportion of breast cancer is rising in India. It presents at a younger age in India as compared to the western countries. This is a retrospective study of 86 breast cancer patients less than 40 years treated in a single center from June 2006 to June 2011. The aim was to assess the factors that may influence clinical outcome. Data were collected from medical records. Variables such as age, stage, surgery, chemotherapy, tumor size, grade, nodal status, perinodal extension, lymphovascular emboli, estrogen receptor, progesterone receptor, and HER-2 neu were analyzed in relation to outcome. Out of total 613 breast cancer patients, 91 (14.8%) were younger than 40 years. Five were excluded due to incomplete data; hence, 86 patients were included in this study. Median tumor size was 3 cm and lymph node positivity was 56.9%. Lymphovascular emboli were positive in 48.8% and perinodal extension was positive in 41.8%. Estrogen receptor positivity was 34.8%, progesterone receptor positivity was 45.3%, and triple negativity was 45.3%. The median follow-up period was 27 months with disease free survival being 73.2% and overall survival being 87.2%. In univariate analysis, the factors significantly associated with survival were stage at presentation, presence of lymphovascular emboli, perinodal extension and grade of the tumor. In multivariate analysis grade of tumor was the only significant factor. In young women with breast cancer, the factors significantly associated with survival were clinical stage at presentation, the presence of lymphovascular emboli and perinodal extension and grade of tumor.

Potential Use of Biomarkers to Augment Clinical Decisions for the Early Detection of Breast Cancer

Breast cancer remains a significant worldwide health problem, despite the fact that early detection is associated with excellent survival rates. Currently, a substantial proportion of breast cancers are not detected using routine screening. Therefore, there is a need to identify a technology that can improve the precision and accuracy of early breast cancer detection. Biomarkers are attractive in that they can potentially detect early cancers with high sensitivity, while distinguishing between benign disease and invasive cancers. Many commonly used serum biomarkers have limited use in screening assays for breast cancer as single agents due to the heterogeneous nature of breast cancer. However, the use of protein panels that detect multiple serum biomarkers offer the potential for enhanced sensitivity and specificity in a clinical setting. Recently, a serum biomarker test comprising five serum biomarkers for breast cancer was clinically validated and showed high sensitivity and specificity. Additional panels have been developed that combine serum protein biomarkers (SPB) and tumor-associated autoantibodies (TAb) to further enhance the clinical utility of the assay. Serum biomarkers are currently not the standard of care and are not recommended in any detection guidelines. However, tumor biomarkers are used in the breast cancer setting to determine the course of care. The purpose of this article is to review recent advances in SPB, TAb, and biomarkers used in breast cancer detection to provide a perspective on how these technologies may offer benefit when combined with current imaging modalities.

Abstract P6-04-03: ERb and breast cancer: A potential predictive and prognostic biomarker and novel therapeutic drug target

Abstract Background: Estrogen receptor beta (ERβ), unlike ERα, classically functions as a tumor suppressor in vitro. However, ERβ's biological functions in vivo and predictive/prognostic value in breast cancer are controversial. Methods: Expression of ERβ protein was determined using a well characterized and validated ERβ specific monoclonal antibody that only recognizes the full-length form of this receptor (PPG5/10) in the following 3 cohorts: 1) a cohort with all breast cancer subtypes (n = 182), 2) a prospective NCCTG adjuvant tamoxifen trial for postmenopausal women with ERα positive breast cancer with long-term follow-up (n = 198) and 3) a cohort of 80 triple negative breast cancers (TNBCs). To elucidate the biological functions of ERβ in breast cancer, novel ERβ expressing MCF7 and MDA-MB-231 cell lines were developed and characterized using multiple techniques and were examined for responsiveness to various ERβ targeted therapies. Results: About one-third of all breast tumors, regardless of sub-type, were shown to express nuclear ERβ and this expression was independent of ERα or HER2. In the NCCTG 89-30-52 cohort, breast cancer recurrence rates were significantly associated with ERβ protein expression with 10 year recurrence rates of 25%, 15% and 4% for zero, low or high levels of ERβ expression respectively. Interestingly, in TNBCs, nuclear ERβ was expressed at intermediate or high levels in 24% of tumors. In the triple negative MDA-MB-231 cell line, expression of ERβ led to inhibition of proliferation and induction of apoptosis in response to estrogen and multiple ERβ specific agonists. Conversely, these same treatments induced proliferation of ERβ-expressing MCF7 cells which endogenously express ERα. However, ERβ expression sensitized MCF7 cells to the anti-proliferative effects of anti-estrogens. Microarray analysis and RT-PCR profiling of MDA-MB-231-ERβ cells revealed that estrogen and ERβ agonists highly induced the expression of multiple cystatins, a family of small secreted cysteine protease inhibitors which function as tumor suppressors, and potently inhibited canonical TGFβ signaling. Conditioned media isolated from estrogen or ERβ agonist treated MDA-MB-231-ERβ cells suppressed the proliferation rates and inhibited TGFβ signaling in other TNBC cell lines, effects that were completely reversed following the depletion of cystatins from the conditioned media. Conclusions: These data demonstrate that ERβ is expressed in a substantial proportion of breast cancers and may have value as a predictive and/or prognostic biomarker. Therapeutic targeting of ERβ may have clinical benefit in multiple breast cancer sub-types; however, the specific drug of choice may vary based on ERα status. Specifically, we have demonstrated that ERβ expression in ERα+ MCF7 cells sensitizes them to the effectiveness of anti-estrogens, an observation that was confirmed in women enrolled in a prospective adjuvant tamoxifen trial. In TNBCs, where targeted therapies are lacking, our data suggest that targeting ERβ with either estrogen or ERβ specific agonists will elicit anti-tumor effects through the induction of cystatins and inhibition of TGFβ signaling resulting in tumor regression and improved patient outcomes. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-04-03.

Clinical Features in Association with Neurodegenerative Diseases and Malignancies

Objective: To examine whether there are clinical features in Japanese patients with both neurodegenerative diseases and cancers. Methods: We analyzed the clinical characteristics of consecutive Japanese patients with neurodegenerative diseases during the past 5 years, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), dementia with Lewy bodies, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA). Results: Out of 292 patients, 39 patients had cancers, including a past history, as follows: ALS, n = 16; PD, n = 8; PSP, n = 7; CBD, n = 1, and MSA, n = 7. About 10% of patients with neurodegenerative diseases developed cancer after onset of the disease; about 30% of patients with ALS, PD, or PSP occurring with cancers died of cancer. Gastric cancer was most common before the onset of ALS (62.5%) but did not develop after the onset of ALS. Conversely, PD patients frequently developed gastric cancers after the onset of neurological signs (60.0%) in spite of no cancer before the onset of PD. The proportion of breast cancer in MSA (45.5%) was significantly higher than in other neurodegenerative diseases. Conclusion: ALS, PD, or MSA patients with cancer showed clinical characteristics unique to each neurodegenerative disease in Japan compared to other countries.