Stage at breast cancer diagnosis is more advanced in BRCA1 carriers but not in BRCA2 carriers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10540-10540
Author(s):  
B. Kaufman ◽  
A. Lahad ◽  
M. Krieger ◽  
M. Gal ◽  
E. Friedman ◽  
...  

10540 Background: BRCA1-associated tumors are known to have less favorable pathological characteristics, but there is little information on whether this is also reflected in the stage at diagnosis. Methods: Clinical and pathological information was collected on 1,122 consecutive Ashkenazi Jewish breast cancer patients who were tested post-diagnosis for the BRCA1/2 mutations common in this population. Results: Of 1,122 patients, 70 (6.2%) were BRCA1 and 50 (4.5%) were BRCA2 carriers. Mean age at diagnosis was 49.9 yrs. in BRCA1 carriers (p=.0001 vs. non-carriers (NC)) vs. 52.0 yrs. in BRCA2 carriers (p=.02 vs. NC) and 56.0 yrs. in NC. Pure DCIS was less common in BRCA1 carriers (3%) than in BRCA2 carriers (8.2%) and NC (11.8%) (p=.03). Medullary carcinoma was more common in BRCA1 (9.8%) and BRCA2 carriers (6.7%) than in NC (1.5%) (p<.001). Invasive lobular carcinomas were rarer in BRCA1 (1.6%) and BRCA2 (2.2%) compared to NC (8.8%) (p=.012). Hormone receptors (HR) negative was more common in BRCA1 (62%) compared to BRCA2 carriers (21%) (p=.00006) and NC (17%) (p<0.0001). Triple negative tumors (HR and HER2 negative) were more common in BRCA1 carriers (60%) than in BRCA2 carriers (14%) and NC (8.3%) (p=0.001). High grade was more common in BRCA1 (60.4%) and BRCA2 (51.4%) carriers than in NC (36.7%, p=.001). Less favorable pathological features and younger age at diagnosis in BRCA1 carriers were reflected in a more advanced stage at diagnosis. Stage I at diagnosis was found in 34% of BRCA1 carriers (p=.05 vs. NC), 43% of BRCA2 carriers and 46% of NC, stage II in 48% of BRCA1 carriers, 41% of BRCA2 carriers and 37% of NC, and stage III in 17% of BRCA1 carriers, 13.5% of BRCA2 carriers and 13.5% of non-carriers. Conclusions: This consecutive cohort study demonstrates that breast cancers in BRCA1 carriers are characterized by more aggressive pathological features and are diagnosed at more advanced stages than in BRCA2 carriers and non-carriers. This may suggest a differential approach for prevention and surveillance in BRCA1 compared to BRCA2 carriers. No significant financial relationships to disclose.

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Rohini K. Bhatia ◽  
Mohan Narasimhamurthy ◽  
Yehoda M. Martei ◽  
Pooja Prabhakar ◽  
Jeré Hutson ◽  
...  

Abstract Background To characterize the clinico-pathological features including estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu (HER2) expression in breast cancers in Botswana, and to compare them by HIV status. Methods This was a retrospective study using data from the National Health Laboratory and Diagnofirm Medical Laboratory in Gaborone from January 1, 2011 to December 31, 2015. Clinico-pathological details of patients were abstracted from electronic medical records. Results A total of 384 unique breast cancer reports met our inclusion criteria. Of the patients with known HIV status, 42.7% (50/117) were HIV-infected. Median age at the time of breast cancer diagnosis was 54 years (IQR 44–66 years). HIV-infected individuals were more likely to be diagnosed before age 50 years compared to HIV-uninfected individuals (68.2% vs 23.8%, p < 0.001). The majority of patients (68.6%, 35/51) presented with stage III at diagnosis. Stage IV disease was not presented because of the lack of data in pathology records surveyed, and additionally these patients may not present to clinic if the disease is advanced. Overall, 68.9% (151/219) of tumors were ER+ or PR+ and 16.0% (35/219) were HER2+. ER+ or PR+ or both, and HER2- was the most prevalent profile (62.6%, 132/211), followed by triple negative (ER−/PR−/HER2-, 21.3%, 45/211), ER+ or PR+ or both, and HER2+, (9.0%, 19/211) and ER−/PR−/HER2+ (7.1%, 15/211). There was no significant difference in receptor status noted between HIV-infected and HIV-uninfected individuals. Conclusions Majority of breast cancer patients in Botswana present with advanced disease (stage III) at diagnosis and hormone receptor positive disease. HIV-infected breast cancer patients tended to present at a younger age compared to HIV-uninfected patients. HIV status does not appear to be associated with the distribution of receptor status in breast cancers in Botswana.


2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 22-22
Author(s):  
Reiko Yoshida ◽  
Mayuko Inuzuka ◽  
Tomoko Watanabe ◽  
Junko Yotsumoto ◽  
Takashi Kuwayama ◽  
...  

22 Background: Hereditary breast and ovarian cancer (HBOC) is a high-penetrance inherited disease, and founder mutation has been reported in the West. However, there are yet no reports of founder mutation of HBOC on breast cancer in the Japanese population. In this study, we report the breast cancer clinical characteristics of L63X, which is one of the founder mutations in BRCA1 in the Japanese population. Methods: Data on 223 affected breast cancer patients (28 BRCA1 carriers, 19 BRCA2 carriers, and 176 non-carriers) were collected at Showa University in Tokyo from September 2010 to June 2015. In 22 independent mutations of BRCA1, the L63X mutation was detected in 9 patients. Data regarding the age of breast cancer onset, pathological features, clinical features, and family history were collected. Results: The age of onset was no significant differences between the L63X mutation and other BRCA1 mutations (39.7 vs. 38.5years). The proportion of triple negative breast cancer patients was 87.5% in the L63X mutation carriers and 89.5% in other BRCA1 mutation carriers. No patients of the L63X affected bilateral breast cancers. On the other hand, 36.7% of other BRCA1mutations affected bilateral breast cancers. There was no significant difference in pathological features (intrinsic subtype, nuclear grade and ki-67 index). The L63X carriers tended to have a family history of breast cancers. All L63X mutations were detected in the Eastern part of Japan. Conclusions: The breast cancer clinical characteristics of L63X might be considered no different from other types of BRCA1 mutations. Recently, it has been reported that breast and ovarian cancer risks varied according to the type and location of BRCA1/2 mutations. L63X mutation is located in the breast cancer cluster region in BRCA1. Further investigation is necessary for appropriate validation and accumulation of data.


2020 ◽  
Author(s):  
Kiyomi Mitsui ◽  
Motoki Endo ◽  
Yuya Imai ◽  
Yuito Ueda ◽  
Hiroko Ogawa ◽  
...  

Abstract Background The number of breast cancer patients of working age is increasing in Japan . Consequently, there is a need for support for working individuals concomitantly undergoing breast cancer treatment. The present study aimed to clarify the risk factors for resignation and taking sick leave among breast cancer survivors in continued employment at the time of diagnosis. Methods As part of a Japanese national research project (Endo-Han), the investigators conducted a web-based survey of cancer survivors (CSs) in 2018. The investigators analyzed the risk factors for post-breast cancer diagnosis resignation and sick leave using a logistic regression model, including age at diagnosis, educational level, cancer stage, surgery, pharmacotherapy, radiotherapy, employment status, and occupational type. Results 40 of 269 breast cancer survivors (14.9%) quit their job after cancer diagnosis. Predictors of resignation included lower education level (odds ratio [OR]: 3.802; 95%CI: 1.233-11.729), taking sick leave (OR: 2.514; 95%CI: 1.202-5.261), and younger age at diagnosis (OR: 0.470; 95%CI: 0.221-0.998). Of 229 patients who continued working, sick leave was taken by 72 (31.4%); having surgery was a predictor for taking sick leave (OR: 8.311; 95%CI: 1.007-68.621). Conclusions 14.9% of Japanese employees quit their jobs after being diagnosed with breast cancer. Being younger at breast cancer diagnosis, having lower educational attainment level, and utilizing sick leave were identified as predictors of post-cancer diagnosis resignation. Surgery was associated with the highest risk of taking sick leave. Breast cancer survivors exhibit higher risks for resignation, and may require more carefully follow-up after diagnosis by healthcare providers and employers to protect work sustainability.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19146-e19146
Author(s):  
Ying Liu ◽  
Aliza Gordon ◽  
Michael Eleff ◽  
John Barron ◽  
Winnie Chi

e19146 Background: Guidelines for optimal frequency of screening mammography (annual, biennial, never/choice of patient) vary by professional society, due to mixed or insufficient evidence regarding its benefits and harms. Little evidence exists on the impact of screening frequency, rather than any screening, on health outcomes. In this study, we measured differences in cancer stage at diagnosis, treatment rendered, mortality, and cost of treatment for women with different numbers of screenings prior to breast cancer diagnosis. Methods: Utilizing administrative claims, we identified 25,492 women aged 44 or older with various numbers of mammographic screening ≥ 11 months apart during the four years prior to their incident breast cancer diagnosis from 2010 to 2018. Outcomes were assessed during the six months following diagnosis. Regression models were used to compare women with differing numbers of mammograms (0, 1, 2, 3, or 4/5), adjusting for demographic characteristics and baseline comorbidities. Results: More screenings were associated with less advanced cancer at diagnosis, higher rates in lumpectomy and radiation, lower rates in mastectomy and chemotherapy, lower costs and mortality within 6 months post diagnosis (Table). Results were similar in a subgroup with only women aged 44-49 at diagnosis (not shown). Conclusions: Increased frequency of screening mammography is associated with earlier breast cancer stage at diagnosis, less toxic and invasive treatment, lower mortality, and lower cost, including for women under age 50. [Table: see text]


2021 ◽  
pp. 153537022199109
Author(s):  
Stephanie Colón-Marrero ◽  
Shirley Jusino ◽  
Yainyrette Rivera-Rivera ◽  
Harold I Saavedra

Biological therapies against breast cancer patients with tumors positive for the estrogen and progesterone hormone receptors and Her2 amplification have greatly improved their survival. However, to date, there are no effective biological therapies against breast cancers that lack these three receptors or triple-negative breast cancers (TNBC). TNBC correlates with poor survival, in part because they relapse following chemo- and radio-therapies. TNBC is intrinsically aggressive since they have high mitotic indexes and tend to metastasize to the central nervous system. TNBCs are more likely to display centrosome amplification, an abnormal phenotype that results in defective mitotic spindles and abnormal cytokinesis, which culminate in aneuploidy and chromosome instability (known causes of tumor initiation and chemo-resistance). Besides their known role in cell cycle control, mitotic kinases have been also studied in different types of cancer including breast, especially in the context of epithelial-to-mesenchymal transition (EMT). EMT is a cellular process characterized by the loss of cell polarity, reorganization of the cytoskeleton, and signaling reprogramming (upregulation of mesenchymal genes and downregulation of epithelial genes). Previously, we and others have shown the effects of mitotic kinases like Nek2 and Mps1 (TTK) on EMT. In this review, we focus on Aurora A, Aurora B, Bub1, and highly expressed in cancer (Hec1) as novel targets for therapeutic interventions in breast cancer and their effects on EMT. We highlight the established relationships and interactions of these and other mitotic kinases, clinical trial studies involving mitotic kinases, and the importance that represents to develop drugs against these proteins as potential targets in the primary care therapy for TNBC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeanne P. Uyisenga ◽  
Ahmed Debit ◽  
Christophe Poulet ◽  
Pierre Frères ◽  
Aurélie Poncin ◽  
...  

AbstractCirculating microRNAs are non-invasive biomarkers that can be used for breast cancer diagnosis. However, differences in cancer tissue microRNA expression are observed in populations with different genetic/environmental backgrounds. This work aims at checking if a previously identified diagnostic circulating microRNA signature is efficient in other genetic and environmental contexts, and if a universal circulating signature might be possible. Two populations are used: women recruited in Belgium and Rwanda. Breast cancer patients and healthy controls were recruited in both populations (Belgium: 143 primary breast cancers and 136 healthy controls; Rwanda: 82 primary breast cancers and 73 healthy controls; Ntot = 434), and cohorts with matched age and cancer subtypes were compared. Plasmatic microRNA profiling was performed by RT-qPCR. Random Forest was used to (1) evaluate the performances of the previously described breast cancer diagnostic tool identified in Belgian-recruited cohorts on Rwandan-recruited cohorts and vice versa; (2) define new diagnostic signatures common to both recruitment sites; (3) define new diagnostic signatures efficient in the Rwandan population. None of the circulating microRNA signatures identified is accurate enough to be used as a diagnostic test in both populations. However, accurate circulating microRNA signatures can be found for each specific population, when taken separately.


2020 ◽  
Author(s):  
Kiyomi Mitsui ◽  
Motoki Endo ◽  
Yuya Imai ◽  
Yuito Ueda ◽  
Hiroko Ogawa ◽  
...  

Abstract Background The number of breast cancer patients of working age is increasing in Japan . Consequently, there is a need for support for working individuals concomitantly undergoing breast cancer treatment. The present study aimed to clarify the risk factors for resignation and taking sick leave among breast cancer survivors in continued employment at the time of diagnosis. Methods As part of a Japanese national research project (Endo-Han), the investigators conducted a web-based survey of cancer survivors (CSs) in 2018. The investigators analyzed the risk factors for post-breast cancer diagnosis resignation and sick leave using a logistic regression model, including age at diagnosis, educational level, cancer stage, surgery, pharmacotherapy, radiotherapy, employment status, and occupational type. Results 40 of 269 breast cancer survivors (14.9%) quit their job after cancer diagnosis. Predictors of resignation included lower education level (odds ratio [OR]: 3.802; 95%CI: 1.233-11.729), taking sick leave (OR: 2.514; 95%CI: 1.202-5.261), and younger age at diagnosis (OR: 0.470; 95%CI: 0.221-0.998). Of 229 patients who continued working, sick leave was taken by 72 (31.4%); having surgery was a predictor for taking sick leave (OR: 8.311; 95%CI: 1.007-68.621). Conclusions 14.9% of Japanese employees quit their jobs after being diagnosed with breast cancer. Being younger at breast cancer diagnosis, having lower educational attainment level, and utilizing sick leave were identified as predictors of post-cancer diagnosis resignation. Surgery was associated with the highest risk of taking sick leave. Breast cancer survivors exhibit higher risks for resignation, and may require more carefully follow-up after diagnosis by healthcare providers and employers to protect work sustainability.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10525-10525
Author(s):  
M. Litwiniuk ◽  
V. Filas ◽  
J. Moczko ◽  
R. Kaleta ◽  
J. Breborowicz

10525 Background: HER-2/neu gene is amplified and overexpressed in 15–20% of invasive breast cancers. HER2-positive breast cancers have a worse prognosis than HER2-negative tumors and distinctive clinical features. They express hormone receptors for estrogen (ERα) and for progesterone (PgR) less frequently than HER2-negative tumors. The identification of the other human estrogen receptor, receptor beta (ERβ), raises a question of ERβ occurrence in HER2-positive breast cancer. Patients and methods: Formalin-fixed, paraffin embedded tissues from 90 patients with invasive HER2-positive breast cancer and from 99 patients with HER2-negative breast cancer were used in this study. The HER2 status was analyzed using HercepTest TM (IHC), and IHC 2+ results were confirmed with FISH test. Immunostaining for ERα, ERβ and PgR was performed using monoclonal antibodies against ERα, PgR (DakoCytomation) and against ERβ (CHEMICON). The EnVision detection system was applied. The data were analyzed using nonparametric Fisher-Freeman-Halton test; the statistical significance was considered when p < 0.5. Results: Only 33% of the HER2-positive breast cancers were ERα-positive compared with 63% in the HER2-negative group (p < 0.001). The expression of ERβ protein was observed in almost equal frequency in both groups (57% of HER2-positive breast cancers and 57.7% of HER2-negative tumors, p = 0.889). The expression of PgR was observed in 30% of HER2-positive breast cancers and in 68.7% of HER2-negative tumors (p < 0.001). Conclusion: The expression of ERβ (unlike that of ERα and PgR) was similar in HER2-positive and in HER2-negative breast cancers. Thus, ERβ may be a potential target in future endocrine therapy for women with HER2-positive breast cancers. No significant financial relationships to disclose.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 639-639
Author(s):  
M. Santarpia ◽  
G. Altavilla ◽  
M. Margeli ◽  
M. Mesiti ◽  
V. Cavallari ◽  
...  

639 Background: Somatic mutations in phosphoinositide-3-kinase catalytic alpha (PIK3CA) activates Akt, attenuates apoptosis and promotes tumor invasion. The common mutations E545K and H1047R confer resistance to paclitaxel in immortalized breast cancer cell lines. We screened primary breast cancers for PIK3CA mutations in the helical and catalytic domains. Methods: Tumor samples from 61 stage I-III breast cancer patients treated with adjuvant chemo- and/or hormone therapy were examined for PIK3CA mutations E542K, E545K and H1047R by the 5-nuclease assay (TaqMan) using the ABI Prism 7900HT Sequence Detection System. Results: Mutations were found in 17 patients (27.9%): 6 E542K; 5 E545K; 6 H1047R. PIK3CA mutations were not associated with expression of estrogen or progesterone receptors, lymph node metastases, or ERBB2 overexpression. (See table ) Conclusions: PIK3CA mutations occur frequently in breast cancer and could be a novel predictive marker of chemoresistance and an appealing target for therapeutic inhibition, independent of hormone receptors and ERBB2 status. [Table: see text] No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 519-519 ◽  
Author(s):  
M. Cheang ◽  
S. K. Chia ◽  
D. Tu ◽  
S. Jiang ◽  
L. E. Shepherd ◽  
...  

519 Background: MA5 randomized premenopausal women with node-positive early breast cancers to cyclophosphamide- methotrexate-fluorouracil (CMF) or cyclophosphamide-epirubicin-fluorouracil (CEF) adjuvant chemotherapy. This and other trials have shown that adjuvant regimens containing anthracyclines confer significant survival benefit to breast cancer patients. Meta-analyses have revealed most benefit in women with HER2(+) or TOPO2 (+) tumors. Population-based data suggest that patients with a core basal phenotype (negative for hormone receptors and HER2, positive for CK5/6 or EGFR) conversely have worse survival on anthracycline containing vs. CMF regimens. Here we test the hypothesis specified a priori that for basal breast cancers anthracyclines may be inferior, using data from MA5. Methods: From 710 patients in MA5, blocks suitable for tissue microarray construction were recovered for 549. Immunohistochemistry for ER, PR, HER2, Ki67, CK5/6 and EGFR was obtained, allowing stratification of 511 cases into intrinsic biological subtypes by published methods (Cheang MC et al. Clin Cancer Res 2008;14:1368–76). Prespecified analyses were conducted independently by the NCIC- CTG statistical centre. Results: In the CEF arm, patients with core basal tumors had a hazard ratio of 1.8 (log rank p=0.02) for overall survival (OS) relative to the other biological subtypes. In the CMF arm, there was no significant difference (HR 0.9, p = 0.7). The interaction between core basal status and treatment was borderline significant (p=0.06). Relapse free survival differences did not reach significance. Conclusions: Data from this randomized trial supports the hypothesis that anthracycline containing adjuvant chemotherapy regimens are inferior to adjuvant CMF in women with basal breast cancer. [Table: see text] No significant financial relationships to disclose.


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